Benefit-risk assessment (BRA) is critical for decision-making throughout the vaccine life cycle. It requires scientific assessment of evidence to make an informed judgment on whether the vaccine has a favourable benefit-risk profile i.e. the benefits of the vaccine outweigh its risks for use in its intended indication. The assessment must also consider data gaps and uncertainties, using sensitivity analyses to show the impact of these uncertainties in the assessment. The BRA field has advanced considerably over the past years, including the use of structured BRA frameworks, quantitative BRA models and use of the patient experience data. Analytical tools and procedures to standardize BRA implementation have become increasingly important. A Benefit-Risk Assessment Module has been prepared to enable the planning, assessment, and communication of relevant BRA information via a structured B-R framework. The module can help facilitate the conduct and communication of defensible BRAs by vaccine developers, funders, regulators and policy makers in high, middle or low-income countries, both for regulatory submissions and in public health responses to infectious diseases, including for epidemics.

Those who refuse immunizations are risks to the public health. Others who are vaccine reluctant are also problematic because they may reinforce the uncertainties of others and refuse vaccines in the future. Common to the multiple, complex causes of vaccine reluctance and refusal is the fact that many have little knowledge about microbiology, infectious diseases, or public health. Consequently, it is not surprising that many have questions about vaccines, find making vaccine decisions difficult, and are vulnerable to vaccine misinformation. Therefore, improving the knowledge of consumers about these biologic sciences would seem to be essential to begin addressing vaccine reluctance and refusal. This would be most effective if it were accomplished before they need to begin to make vaccine decisions.

BACKGROUND: Relative effectiveness of various vaccine formulations provide important input for vaccine policy decisions and provider purchasing decisions. We used electronic databases to conduct a test-negative case control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine (RIV4) compared with standard dose vaccines (SD-IIV4) against influenza hospitalization. METHODS: Adults 18-64 and ≥65 years of age hospitalized in a large U.S. health system (19 hospitals) in 2018-2019 and 2019-2020 who were clinically tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays were included. The hospital system electronic medical record (EMR) and the state immunization registry were used to confirm influenza vaccination. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. RESULTS: Of the 14,590 individuals included in the primary analysis, 3,338 were vaccinated with RIV4 and 976 were vaccinated with SD-IIV4, with the balance of 10,276 being unvaccinated. Most participants were white (80 %), most (70 %) had a high-risk condition, just over half were female (54 %) and age 65 years or older (53 %). Overall RIV4 rVE was significant when adjusted for propensity scores with inverse probability weights (rVE = 31; 95 % CI = 11 %, 46 %). Among younger adults (18-64 years-old), overall rVE of RIV4 was significant (rVE = 29; 95 % CI = 4 %, 47 %). CONCLUSIONS: Over all adults, both RIV4 and SD-IIV4 were effective against influenza hospitalization, with RIV4 providing better protection compared with SD-IIV4 overall, for females, younger adults, and those with no high-risk conditions.

An enzyme linked immunosorbent assay (ELISA) method was developed to analyze the assembly of a tetravalent mosaic influenza nanoparticle (NP) vaccine, Flumos-v1, consisting of hemagglutinin trimers (HAT) from H1 (A/Idaho/07/2018), H3 (A/Perth/1008/2019), HBV (Vic-B/Colorado/06/2017) and HBY (Yam-B/Phuket/3073/2013) strains. The sandwich ELISA assay used lectin from Galanthus nivalis as a universal capture reagent for all HAT strains and specific monoclonal antibody (mAb) to detect corresponding hemagglutinin antigen. The mAb binding of HATs incorporated into NPs diverged from those for single HAT solutions, resulting in inaccurate quantitation of assembled HATs. An optimized zwittergent treatment was used to fully dissociate the influenza NP and aligned binding activities in each pair of single HAT and dissociated HAT from NP. The dissociated HATs were then quantified against their corresponding HAT standard solutions for three development lots of FluMos-v1 vaccine and the assembly ratio of all four HATs was calculated. The molar ratio of different HATs incorporated into this quadrivalent NP vaccine was consistent and determined as H3:H1: HBV: HBY ∼ 1.00:0.92:0.96:0.87, which was close the expected 1:1:1:1 ratio and confirmed a proper assembling of multivalent NP.

The continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ+ T-cell response. We conclude that PHH-1V is safe and elicits a robust immune response to SARS-CoV-2 in pigs, a large animal preclinical model.

BACKGROUND: In the Republic of Korea (Korea), the NVX-CoV2373 (Novavax) coronavirus disease 2019 (COVID-19) vaccination was administered to 18-year-olds and over from February 14, 2022. This study sought to assess the frequency and severity of reported adverse events following the Novavax COVID-19 vaccination in Korea. METHODS: Adverse events based on two national vaccine safety data were analyzed; the COVID-19 vaccination management system (CVMS) and the text-message survey (TMS). RESULTS: CVMS identified that the reporting rate of adverse events per 100,000 doses were lower after booster doses (84.0) than after dose 1 (254.6) or dose 2 (272.9); and in 65-year-olds and over (83.4) than in 18- to 64-year-olds (168.1). The TMS found that local and systemic adverse events were lower in 65-year-olds and over than in 18- to 64-year-olds (p < 0.001). CONCLUSIONS: Overall, we identified no major safety issues and fewer adverse events following the Novavax COVID-19 vaccination among 65-year-olds and over in Korea.

OBJECTIVES: We aimed to identify and explore the association between the characteristics of coronavirus disease 2019 (COVID-19) vaccine recipients and the types of vaccine-related adverse effects in the general Japanese adult population. METHODS: An anonymous self-report questionnaire was distributed to 4393 students and 1657 white and blue-collar workers (N = 6050). Data on vaccine-related adverse effects were collected twice, once after each vaccination. The data collection was performed daily from the day of injection (D0) until the sixth day after injection (D6). The list of adverse effects comprised local reactions at the injection site (pain, redness, and swelling) and systemic symptoms (fever, fatigue, headache, myalgia, joint pain, chills, and nausea or vomiting). The Student's t-test and Mann-Whitney U test were used to analyze parametric and non-parametric data, respectively. RESULTS: The incidence of adverse reactions to the COVID-19 vaccination was higher after the second dose (e.g., redness: 47.1%; swelling: 60.6%; fever: 80.6%) of vaccination than after the first dose (e.g., redness: 16.4%; swelling: 37.2%; fever: 11.9%). Women reported adverse reactions to the vaccination more frequently. Some adverse reactions included more symptoms in younger participants, and participants with a lower body mass index were more at risk for these symptoms. CONCLUSIONS: Some adverse reactions to the COVID-19 vaccination are a greater risk of symptoms in the younger group, women, and participants with lower BMI. Care should be taken to monitor women, younger people, and individuals with a low body mass index for adverse effects after receiving the COVID-19 vaccination.

Bovine ephemeral fever virus (BEFV) is a globally spread arthropod-borne RNA virus that has significant economic impacts on the cattle industry. A live attenuated commercial BEF vaccine, based on the Australian BEFV strain 919, is widely used in Israel and other countries. A previous study has suggested the high effectiveness of this vaccine (ULTRAVAC BEF VACCINE™ from Zoetis®), but anecdotal reports of high BEF morbidity among vaccinated dairy herds in Israel casted doubt on these findings. To resolve this uncertainty, a randomized controlled field vaccine effectiveness study was conducted in Israel during a BEF outbreak which occurred in 2021. Eleven dairy herds were enrolled and monitored for BEF-associated morbidity and rumination alteration patterns using electronic monitoring tags (HR Tags, SCR® Dairy, Netanya, Israel). Four of the herds were naturally infected with BEFV during the outbreak, resulting in a total of 120 vaccinated and 311 unvaccinated subjects that were included in the effectiveness study. A mixed-effect Cox proportional hazard regression model was used to calculate the overall hazard ratio between vaccinated and unvaccinated cattle. This analysis demonstrated an average vaccine effectiveness of 60 % (95 % CI = 38 %-77 %) for preventing clinical disease. In addition, a non-statistically significant trend (p = 0.1) towards protection from mortality was observed, with no observation of mortality among the vaccinated groups compared to 2.61 % mortality (7/311) among the unvaccinated subjects. One hundred and thirty vaccinated and unvaccinated calves from affected and non-affected herds and with different status of morbidity were sampled and analysed by serum-neutralization test. The highest titers of BEFV-neutralizing antibodies were found in subjects that were both vaccinated and clinically affected, indicating a booster effect after vaccination. The results of the study provide evidence for the moderate effectiveness of the ULTRAVAC BEF VACCINE™ for the prevention of BEF.

BACKGROUND: Several randomized trials and real-world studies depicted the role of monoclonal antibody infusion in reducing hospitalization, and halting progression from asymptomatic to symptomatic COVID pneumonia, viral titer, and death. No data exists to show outcomes of patients who received casirivimab-imdevimab infusion based on their vaccination status and underlying comorbidities. This study aims to provide outcomes of casirivimab-imdevimab treatment during the SARS-CoV-2 B1.617.2 (Delta) surge among fully vaccinated and not fully vaccinated individuals. METHODS: COVID-19-positive patients who received casirivimab-imdevimab infusion during the Delta surge were analyzed to compare their underlying comorbidities and the rate of 28-days all-cause and COVID-related ED visits or hospitalization, among fully vaccinated and not fully vaccinated individuals. RESULTS: A total of 3,586 patients received casirivimab-imdevimab infusion. COVID-related hospitalizations were directly related to the number of comorbidities (OR:1.745, 95 % CI:1.469-2.074). Vaccinated patients with ≥3 comorbidities had lower rates of 28-day COVID-related ED visits or hospitalization (p = 0.044) and those with ≥4 comorbidities had lower rates of 28-day All-cause ED visits or hospitalization (p = 0.029). Hypertension (OR:2.418, 95 %CI:1.341-4.360), immunocompromised state (OR:5.250, 95 %CI: 1.912-14.417), age ≥ 65 (OR:4.045, 95 %CI:2.224-7.358) increased the probability of hospitalization due to COVID and being fully vaccinated lowered the likelihood of hospitalization (OR: 0.472, 95 %CI: 0.239-0.933). Vaccinated patients had a lower length of COVID-related hospitalization (2 days vs 4.5 days, p < 0.001). CONCLUSION: COVID vaccination status and comorbidities are significant predictors of outcomes after casirivimab-imdevimab treatment. Despite having higher comorbidities, patients who were fully vaccinated at the time of casirivimab-imdevimab infusion had a lower length of hospitalization and reduced 28-day COVID ED visits or hospitalizations. Future trials should also compare outcomes based on the patient's vaccination status.

BACKGROUND: Existing ethics guidance and regulatory requirements emphasize the need for pregnancy-specific safety and efficacy data during the development of vaccines in health emergencies. Our objective was to conduct a systematic review of vaccine clinical trials during active epidemic periods. METHODS: We searched for Phase II and Phase III vaccine clinical trials initiated during the H1N1 influenza, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Zika, and Ebola virus disease (EVD) outbreaks from 2009 to 2019. Data were extracted from clinical trial protocols identified in the following registries: ClinicalTrials.gov, Pan African Clinical Trial Registry (PACTR), and all primary registries indicated by the World Health Organization's International Clinical Trials Registry Platform (ICTRP). Published studies from registered clinical trials were located through PubMed. Data was extracted on eligibility criteria and pregnancy outcomes. Data from this study is available in the Center for Open Science Data Repository: https://osf.io/nfk2p/?view_only=47deb3b206724af9b46c9c0c0083a267. RESULTS: We identified 96 vaccine clinical trial protocols and included 84 in analysis. 5 records were excluded in screening for irrelevant abstracts, 7 were excluded in full-text assessment (1 for a therapeutic drug trial, 3 for enrolling elderly adults only, 3 for enrolling children/adolescents only). There were no eligible trials for MERS-CoV or Zika virus vaccines. Overall, 8 protocols explicitly included pregnant people; of these, 3 were completed trials with published results. Incidental pregnancies and outcomes of pregnant participants were reported in 2 studies, 10 studies reported serious adverse events related to pregnancy without mentioning total incidental pregnancies. A total of 411 recorded pregnancy outcomes were reported, with 293 from the 3 pregnancy-eligible studies with results. 71 serious adverse events pertaining to pregnancy were reported from all clinical trials with results. CONCLUSION: Pregnant people are underrepresented in vaccine clinical trials conducted during outbreaks, resulting in underreporting of pregnancy-related outcomes and a lack of protection for pregnant people and neonates from infectious diseases.

Development of a vaccine drug product requires formulation optimization to ensure that the vaccine's effectiveness is preserved upon storage throughout the shelf-life of the product. Although aluminum adjuvants have been widely used in vaccine formulations to safely and effectively potentiate an immune response, careful attention must be directed towards ensuring that the type of aluminum adjuvant does not impact the stability of the antigenic composition. PCV15 is a polysaccharide-protein conjugate vaccine comprising the pneumococcal polysaccharide (PnPs) serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F), each individually conjugated to the protein carrier CRM197. PCV15 was formulated with either amorphous aluminum hydroxyphosphate sulfate adjuvant (AAHS) or aluminum phosphate adjuvant (AP) and examined for both stability and immunogenicity. Using a collection of methods to evaluate vaccine stability, it was discovered that certain PCV15 serotypes (e.g., 6A, 19A, 19F) formulated with AAHS resulted in a reduction of immunogenicity in vivo and a reduction in recoverable dose as tested by an in vitro potency assay. The same polysaccharide-protein conjugates formulated with AP were stable regarding all measures tested. Moreover, the reduction in potency of certain serotypes correlated with chemical degradation of the polysaccharide antigen caused by the aluminum adjuvant as measured by reducing polyacrylamide gel electrophoresis (SDS-PAGE), High-Pressure Size Exclusion Chromatography coupled with UV detection (HPSEC-UV) and ELISA immunoassay. This study suggests a formulation, which includes AAHS, may negatively impact the stability of a pneumococcal polysaccharide-protein conjugate vaccine that contains phosphodiester groups. This decrease in stability would likely result in a decrease in the "active" concentration of antigen dose, and herein, it is shown that such instability directly compromised vaccine immunogenicity in an animal model. The results presented in this study help to explain critical degradation mechanisms of pneumococcal polysaccharide-protein conjugate vaccines.

INTRODUCTION: The purpose of this study is to examine relationships between COVID-19 vaccination, social processes, and the practical issues of healthcare coverage and workplace requirements. We examine these relationships among individuals who expressed some degree of hesitancy towards receiving the vaccine. Assessing relationships between COVID-19 vaccination, social processes, and practical issues among vaccine-hesitant individuals has implications for public health policy and intervention. METHODS: We analyzed weighted data from a random sample phone survey of Arkansas adults (N = 2,201) between March 1st and March 28th, 2022 and constrained our analytical sample to those who had reported some degree of vaccine hesitancy (N = 1,251). Statistical analyses included weighted and unweighted descriptive statistics, weighted bivariate logistic regressions, and a weighted multivariate logistic regression to obtain adjusted odds ratios for COVID-19 vaccination. RESULTS: More than two-thirds (62.5 %) of respondents were vaccinated, despite their hesitancy. Adjusted odds of COVID-19 vaccination were greater among Black (OR = 2.55; 95 % CI[1.63, 3.97]) and Hispanic respondents (OR = 2.46; 95 % CI[1.53, 3.95]), respondents whose healthcare provider recommended vaccination (OR = 2.50; 95 % CI[1.66, 3.77]), and as perceptions of vaccination coverage (OR = 2.04; 95 % CI[1.71, 2.43]) and subjective social status increased (OR = 1.10; 95 % CI[1.01, 1.19]). Adjusted odds of COVID-19 vaccination were greater among respondents with a workplace that recommended (OR = 1.96; 95 % CI[1.03, 3.72]) or required vaccination (OR = 12.62; 95 % CI[4.76, 33.45]) and among respondents who were not employed (OR = 1.82; 95 % CI[1.10, 3.01]) compared to those whose workplace did not recommend or require COVID-19 vaccination. CONCLUSIONS: Some hesitant individuals become vaccinated despite their hesitancy-a group we refer to as "hesitant adopters." Social processes and practical issues are important correlates of vaccination among those who are hesitant. Workplace requirements appear to be of particular importance for vaccination among hesitant individuals. Provider recommendations, norms, social status, and workplace policies may be effective points of intervention among those who express vaccine hesitancy.

INTRODUCTION: This study aimed to understand barriers and enablers, future strategies, communication approaches and resources needed for COVID-19 vaccination among migrant communities in Melbourne, Australia. MATERIAL AND METHODS: We interviewed 24 immunisation providers who deliver immunisation services to migrant populations in Melbourne. We used the WHO Behavioural and Social Drivers framework (underlined) to organise barriers and enablers to COVID-19 vaccination. RESULTS: Participants believed migrants had concerns about vaccine safety and efficacy and saw vaccines as minimally beneficial in the 'low COVID-19' environment of Australia (what people think and feel). Healthcare providers with established relationships within migrant communities played key roles in vaccine advocacy (social processes). Migrants' vaccine motivation was mediated by health literacy, institutional trust and previous experiences with health services. Practical issues included perceived lack of information on vaccine booking process and accessibility challenges. CONCLUSIONS: Strategies to increase migrant vaccine coverage should utilise immunisation providers with community links and trusted local vaccine ambassadors to engage and address community vaccine concerns.

Low and very-low-birth-weight (V/LBW) neonates are highly susceptible to bacterial sepsis and meningitis. Bacterial infections caused by Staphylococcus aureus can be particularly dangerous for neonates and can result in high mortality and long-term disabilities.Antibody-based strategies have been attempted to protect V/LBW neonates against staphylococcal disease. However, these efforts have so far been unsuccessful. Failures were attributed to the immaturity of the neonatal immune system but did not account for the anti-opsonic activity of Staphylococcal protein A (SpA). Here we show that monoclonal antibody 3F6, which blocks SpA activity, promotes complement-dependent cell-mediated phagocytosis of S. aureus in human umbilical cord blood. A substitution in the crystallizable fragment (Fc) region of 3F6 that enhances recruitment of complement component C1q further increases the phagocytic activity of cord blood. Our data demonstrate that the neonatal immune system possesses bactericidal activity that can be harnessed by antibodies that circumvent a key innate immune strategy of S. aureus.

OBJECTIVES: To investigate in silico the occurrence of epigenetic crosstalk by nucleotide sequence complementarity between the BNT162b2 mRNA vaccine and whole human genome, including coding and noncoding (nc)RNA genes. To correlate these results with those obtained with the original spike (S) gene of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). METHODS: The publicly available FASTA sequence of the BNT162b2 mRNA vaccine and the SARS-CoV-2 isolate Wuhan-Hu-1 S gene (NC_045512.2) were used separately as key input to the Ensembl.org library to evaluate base pair match to human GRCh38 genome. Human coding and noncoding genes harboring hits were assessed for functional activity and health effects using bioinformatics tools and GWAS databases. RESULTS: The BLAT analysis against the human GRCh38 genome revealed a total of 37 hits for BNT162b2 mRNA and no hits for the SARS-CoV-2 S gene. More specifically, BNT162b2 mRNA matched 19 human genes whose protein products are variously involved in enzyme reactions, nucleotide or cation binding, signaling, and carrier functions. In BLASTN analysis of ncRNA genes, BNT162b2 mRNA and SARS-CoV-2 S gene matched 17 and 24 different human genomic regions, respectively. Overall, characterization of the matched noncoding sequences revealed stronger interference with epigenetic pathways for BNT162b2 mRNA compared with the original S gene. CONCLUSION: This pivotal in silico analysis shows that SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. Although they do not share the same complementarity pattern, both may disrupt epigenetic mechanisms in target cells, potentially leading to long-term complications.

BACKGROUND: Globally, RSV is a common viral pathogen that causes 64 million acute respiratory infections annually. Our objective was to determine the incidence of hospitalization, healthcare resource use and associated costs of adults hospitalized with RSV in Ontario, Canada. METHODS: To describe the epidemiology of adults hospitalized with RSV, we used a validated algorithm applied to a population-based healthcare utilization administrative dataset in Ontario, Canada. We created a retrospective cohort of incident hospitalized adults with RSV between September 2010 and August 2017 and followed each person for up to two years. To determine the burden of illness associated with hospitalization and post-discharge healthcare encounters each RSV-admitted patient was matched to two unexposed controls based on demographics and risk factors. Patient demographics were described and mean attributable 6-month and 2-year healthcare costs (2019 Canadian dollars) were estimated. RESULTS: There were 7,091 adults with RSV-associated hospitalizations between 2010 and 2019 with a mean age of 74.6 years; 60.4 % were female. RSV-coded hospitalization rates increased from 1.4 to 14.6 per 100,000 adults between 2010-2011 and 2018-2019. The mean difference in healthcare costs between RSV-admitted patients and matched controls was $28,260 (95 % CI: $27,728 - $28,793) in the first 6 months and $43,721 over 2 years (95 % CI: $40,383 - $47,059) post-hospitalization. CONCLUSIONS: RSV hospitalizations among adults increased in Ontario between 2010/11 to 2018/19 RSV seasons. RSV hospitalizations in adults were associated with increased attributable short-term and long-term healthcare costs compared to matched controls. Interventions that could prevent RSV in adults may reduce healthcare burden.

The B.1.1.529 (Omicron) variant surge has raised concerns about the effectiveness of vaccines and the impact of imprudent reopening. Leveraging over two years of county-level COVID-19 data in the US, this study aims to investigate relationships among vaccination, human mobility, and COVID-19 health outcomes (assessed via case rate and case-fatality rate), controlling for socioeconomic, demographic, racial/ethnic, and partisan factors. A set of cross-sectional models was first fitted to empirically compare disparities in COVID-19 health outcomes before and during the Omicron surge. Then, time-varying mediation analyses were employed to delineate how the effects of vaccine and mobility on COVID-19 health outcomes vary over time. Results showed that vaccine effectiveness against case rate lost significance during the Omicron surge, while its effectiveness against case-fatality rate remained significant throughout the pandemic. We also documented salient structural inequalities in COVID-19-related outcomes, with disadvantaged populations consistently bearing a larger brunt of case and death tolls, regardless of high vaccination rates. Last, findings revealed that mobility presented a significantly positive relationship with case rates during each wave of variant outbreak. Mobility substantially mediated the direct effect from vaccination to case rate, leading to a 10.276 % (95 % CI: 6.257, 14.294) decrease in vaccine effectiveness on average. Altogether, our study implies that sole reliance on vaccination to halt COVID-19 needs to be re-examined. Well-resourced and coordinated efforts to enhance vaccine effectiveness, mitigate health disparity and selectively loosen non-pharmaceutical interventions are essential to bringing the pandemic to an end.

Vaccines for avian influenza (AI) can protect poultry against disease, mortality, and virus transmission. Numerous factors, including: vaccine platform, immunogenicity, and relatedness to the field strain, are known to be important to achieving optimal AI vaccine efficacy. To better understand how these factors contribute to vaccine protection, a systematic meta-analysis was conducted to evaluate efficacy data for vaccines in chickens challenged with highly pathogenic (HP) AI. Data from a total of 120 individual trials from 25 publications were selected and evaluated. Two vaccine criteria were evaluated for their effects on two metrics of protection. The vaccine criteria were: 1) the relatedness of the vaccine antigen and challenge strain in the hemagglutinin 1 domain (HA1) protein sequence; 2) vaccine-induced antibody titers to the challenge virus (VIAC). The metrics of protection were: A) survival of vaccinated chickens vs unvaccinated controls; and B) reduction in oral virus-shedding by vaccinated vs unvaccinated controls 2-4 days post challenge. Three vaccine platforms were evaluated: oil-adjuvanted inactivated whole AI virus, recombinant herpes virus of turkeys (rHVT) vectored, and a non-replicating alpha-virus vectored RNA particle (RP) vaccine. Higher VIAC correlated with greater reduction of virus-shed and vaccine efficacy by all vaccine platforms. Both higher HA1 relatedness and higher VIAC using challenge virus as antigen correlated with better survival by inactivated vaccines and rHVT-vectored vaccines. However, rHVT-vectored and RP based vaccines were more tolerant of variation in the HA1; the relatedness of the HA1 of the vaccine and challenge virus did not significantly correlate with survival with rHVT-vectored vaccines. Protection was achieved with the lowest aa similarity for which there was data, 90-93 % for rHVT vaccines and 88 % for the RP vaccine.

To assess safety in vaccine development, stricter grading scales, such as the "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" issued by the U.S. Food and Drug Administration (FDA grading scale), are required. However, concern exists that their strictness may lead to an overestimation of some adverse events (AEs). We analyzed the details of AEs in a phase I clinical trial of a preventive vaccine for infectious diseases. In this trial, we observed the high occurrence of Grade 1 or greater AEs in hemoglobin changes from baseline value, and hypernatremia, and hypokalemia by FDA grading scale. The range considered as non-AE according to the FDA grading scale shifted or became narrower when compared to reference intervals, especially for a Japanese cohort. For sodium grading, the criterion for hypernatremia was around 2 to mEq/L lower than the upper limit of most standards in several countries. Also, the criterion for hypokalemia was around 0.2 mEq/L higher than the lower limit of most standards. Regarding a decrease in hemoglobin from baseline, the criterion of "any decrease" used for a Grade 1 AE was too strict and we suggest this be omitted. Upper and lower limits of AE criteria for sodium and potassium should be equal to, or 10-20% above, the reference interval consistent with other toxicities determined by laboratory tests. Consideration should be given to the issues surrounding the criteria that determine AEs before conducting clinical trials.

BACKGROUND: The burden of the current COVID-19 pandemic is not shared equally in Canadian society, with Indigenous Peoples being disproportionately affected. Moreover, there is a lack of research pertaining to vaccination behaviour in Métis communities. This Métis-specific and Métis-led qualitative study endeavours to understand COVID-19 vaccine behaviour among citizens of the Métis Nation of Ontario (MNO). METHODS: Data was collected via one-on-one interviews. Participants were recruited via the MNO's existing social media channels. Participants filled out a screening survey indicating their intention to vaccinate against COVID-19 as yes, no, or unsure. Sixteen participants (9 yes, 3 unsure, 4 no) were interviewed. Interviews averaged 30 min, and the questions and probes were developed in collaboration with the MNO. The interviewer received Métis-specific cultural safety training. Interviews were transcribed verbatim and uploaded to NVivo 12. RESULTS: A deductive analysis using the Social Ecological Model framework (SEM) for vaccine behaviour and two blinded coders was used to understand the data. An additional factor, COVID-19 public health measures, was added to the framework to better capture the experiences of participants during the COVID-19 pandemic. Overall, the factors with the greatest number of coded references included Vaccine roll-out and availability, Organization of the public into priority groups, Public discourse, Interpersonal influences, Interface with health professionals, Knowledge state, Trust, and Vaccine risk perception. Bandwagoning (following others' behaviour) and Freeloading (perceiving enough people have been vaccinated), both factors of the SEM, were not discussed. Yes, no, and unsure participant groups were compared to understand the influences of each factor based on COVID-19 vaccination intention. CONCLUSIONS: MNO citizens COVID-19 vaccine behaviour was negatively and positively influenced by a number of factors. This information will allow the MNO and public health units to better tailor their messaging for COVID-19 vaccine uptake campaigns and future pandemic emergencies.

BACKGROUND: The goal of 'Measles and Rubella Strategic Framework 2021-2030' is to make "A world free from measles and rubella". To be a part of this journey, Human Biologicals Institute has developed Mebella™ vaccine, which is a lyophilized Measles and Rubella (Live) vaccine. A randomized, single blind, comparative, multicenter Phase II/III trial was conducted to compare the immunogenicity and safety of Mebella™ vaccine with MR-VAC® vaccine in healthy subjects. METHODS: A total of 888 subjects were enrolled in four age groups (222 subjects in each group) of 18 years to 49 years; 2 years to below 18 years; 12 months to below 24 months; and 9 months to below 12 months of age. The subjects were randomized in 2:1 ratio to receive single dose of either Mebella™ vaccine of Human Biologicals Institute or MR-VAC® vaccine. Immunogenicity was assessed at 42 days after the vaccination and was compared between the vaccine arms in each group. Safety was also assessed and compared between the vaccine arms during the study period. RESULTS: A total of 875 subjects completed the study out of 888 enrolled subjects. The seroprotection rates, seroconversion rates, and geometric mean titres for both Measles and Rubella components of Mebella™ vaccine were found to be comparable and non-inferior to the MR-VAC® vaccine after 42 days of vaccination. Injection site pain was the most common local adverse event reported whereas fever was the only systemic adverse event reported in both the vaccine arms. No serious adverse event was reported. CONCLUSION: It was concluded from the study results that the test vaccine, Mebella™, was immunogenic and well tolerated and was non-inferior to the comparator vaccine, MR-VAC®, when administered to healthy subjects of 9 months to 49 years of age. Clinical Trial Registry of India Identifier: CTRI/2020/07/026930.

Development of next-generation vaccines against Plasmodium falciparum (Pf) is a priority. Many malaria vaccines target the pre-erythrocytic sporozoite (SPZ) and liver stages. These include subunit vaccines based on the Pf circumsporozoite protein (CSP) and attenuated PfSPZ vaccines. However, these strategies require 3-4 doses and have not achieved optimal efficacy against field-transmitted malaria. Prime-and-trap is a recently developed two-step heterologous vaccine strategy that combines priming with DNA encoding CSP followed by a single dose of attenuated SPZ. This strategy aims to induce CD8+ T cells that can eliminate parasites in the liver. Prior data has demonstrated that prime-and-trap with P. yoelii CSP and PySPZ was immunogenic and protective in mice. Here we report preliminary data on the immunogenicity of PfCSP prime and PfSPZ trap vaccine in rhesus macaques. This vaccine induced PfCSP-specific antibodies and T cell responses in all animals. However, response magnitude differed between individuals, suggesting further study is required.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010-2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.

BACKGROUND: Treatment of Neisseria gonorrhoeae is under threat with the emergence and spread of antimicrobial resistance. Thus, there is a growing interest in the development of a gonorrhoea vaccine. We used mathematical modelling to assess the impact of a hypothetical vaccine in controlling gonorrhoea among heterosexuals living in a setting of relatively high N. gonorrhoeae prevalence (∼3 %). METHODS: We developed a mathematical model of N. gonorrhoeae transmission among 15-49-year-old heterosexuals, stratified by age and sex, and calibrated to prevalence and sexual behaviour data from South Africa as an example of a high prevalence setting for which we have data available. Using this model, we assessed the potential impact of a vaccine on N. gonorrhoeae prevalence in the entire population. We considered gonorrhoea vaccines having differing impacts on N. gonorrhoeae infection and transmission and offered to different age-groups. RESULTS: The model predicts that N. gonorrhoeae prevalence can be reduced by ∼50 % in 10 years following introduction of a vaccine if annual vaccination uptake is 10 %, vaccine efficacy against acquisition of infection is 25 % and duration of protection is 5 years, with vaccination available to the entire population of 15-49-year-olds. If only 15-24-year-olds are vaccinated, the predicted reduction in prevalence in the entire population is 25 % with equivalent vaccine characteristics and uptake. Although predicted reductions in prevalence for vaccination programmes targeting only high-activity individuals and the entire population are similar over the same period, vaccinating only high-activity individuals is more efficient as the cumulative number of vaccinations needed to reduce prevalence in the entire population by 50 % is ∼3 times lower for this programme. CONCLUSION: Provision of a gonorrhoea vaccine could lead to substantial reductions in N. gonorrhoeae prevalence in a high prevalence heterosexual setting, even with moderate annual vaccination uptake of a vaccine with partial efficacy.

This review describes the importance of economic evaluations and real-world evidence (RWE) for the assessment of enhanced influenza vaccines for older adults in Europe. Individuals ≥65 years of age are at increased risk of severe influenza outcomes and many countries in Europe recommend enhanced vaccines for this population to mitigate immunosenescence. Some National Immunization Technical Advisory Groups (NITAGs) may preferentially recommend a specific enhanced vaccine, necessitating comparative economic evaluation and estimation of relative vaccine effectiveness between enhanced vaccine options in the absence of direct head-to-head efficacy data. Distinct approaches to economic modeling and cost-effectiveness analysis (CEA) guide national vaccination policies in Europe, including how underlying data, such as RWE, are used in these models. RWE is an important evidence source for input into CEA models based on disease factors (e.g., antigenic shift and seasonal variation) and practical factors (e.g., limitations of performing multiple randomized clinical trials to capture seasonal variation; the need to obtain relevant patient-oriented, real-world endpoints, such as hospitalizations). CEA is considered crucial to vaccine assessment among certain countries in Europe, but further harmonization of economic evaluations, including the use of RWE, across NITAGs in Europe may be of benefit, alongside standardized approaches for vaccine appraisal. In the future, more countries may use RWE as an input in CEA models to support NITAG recommendations for enhanced influenza vaccines in older populations, especially considering the value of RWE for the assessment of influenza epidemiology and vaccine effectiveness as stated by the World Health Organization, and the availability of a broad RWE base for certain enhanced vaccines.

Vaccination procedures can be stressful for fish and can bring severe side effects. Therefore, vaccines that can minimize the number of administrations and maximize cross-protection against multiple serotypes, genotypes, or even different species would be highly advantageous. In the present study, we investigated the cross-protective ability of two types of vaccines - viral hemorrhagic septicemia virus (VHSV) G protein-expressing DNA vaccine and G gene-deleted single-cycle VHSV genotype IVa (rVHSV-ΔG) vaccine - against both VHSV genotype Ia and infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss). The results showed that rainbow trout immunized with VHSV genotype Ia G gene- or IVa G gene-expressing DNA vaccine were significantly protected against VHSV genotype Ia, but were not protected against IHNV. In contrast to the DNA vaccine, the single-cycle VHSV IVa vaccine induced significant protection against not only VHSV Ia but also IHNV. Considering no significant increase in ELISA titer and serum neutralization activity against IHNV in fish immunized with single-cycle VHSV IVa, the protection might be independent of humoral adaptive immunity. The scarcity of cytotoxic T cell epitopes between VHSV and IHNV suggested that the possibility of involvement of cytotoxic T cell-mediated cellular adaptive immunity would be low. The role of trained immunity (innate immune memory) in cross-protection should be further investigated.

This cohort study evaluated the protection against symptomatic Omicron BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original monovalent vaccines (Pfizer- BioNTech or Moderna). Individuals of ≥60 years old, who received a booster dose between 03/10/2022 and 06/11/2022, when both bivalent and monovalent vaccines were used in France, were included and matched according to the type of booster vaccine received. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, ≥ seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136,852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8 % [95 % CI: 0 %-16 %, p = 0.045] against symptomatic Omicron BA.5infection compared to the monovalent vaccines.

BACKGROUND: It is unclear how hesitancy towards pediatric vaccines has changed quantitatively since the onset of the COVID-19 pandemic, and if changes are more readily apparent in clusters of low COVID-19 vaccination. In this study, we assess how clusters of low COVID-19 vaccination correlate with changing parental beliefs about childhood vaccines. METHODS: A cross-sectional, opt-in, internet-based survey of parents resident in the U.S. was conducted during August-September 2022. Our survey measured changes in beliefs about childhood vaccine safety, importance, and effectiveness since the start of COVID-19. We also measured parents' perceived vaccination rates in the community, assessing its relationship with changing vaccination perceptions using Rao-Scott chi-square tests, and multinomial logistic regression models. RESULTS: Among 310 parents of children 0-17 years old, 11 % (95 % CI: 7 %, 15 %) believed that childhood vaccines are less safe, 12 % (95 % CI: 8 %, 17 %) less important, and 13 % (95 % CI: 9 %, 18 %) less effective since the start of the COVID-19 pandemic. About 9 % (95 % CI: 5 %, 12 %) stated COVID-19 vaccination coverage was low in their community. Among those who stated COVID-19 vaccination coverage was low, 38 % reported believing childhood vaccines were less effective (vs 12 % of those who stated vaccination coverage was high). This corresponds to 4.34 times greater odds of believing childhood vaccines were less effective since the start of the pandemic (95 % CI: 1.38, 13.73) in those who believe COVID-19 vaccination coverage to be low in their community vs high. CONCLUSION: Our study demonstrates that parental perceptions about childhood vaccines have been affected by the COVID-19 pandemic through geographic and social clustering of non-vaccination. Beliefs about the COVID-19 vaccine have spillover with beliefs about childhood vaccines, and more negative beliefs may be clustering in areas with low vaccination coverage, which could predispose the area to outbreaks of vaccine-preventable disease.

Salmonella enterica subspecies enterica serovar Typhimurium (S.Tm) poses a considerable threat to public health due to its zoonotic potential. Human infections are mostly foodborne, and pork and pork products are ranked among the top culprits for transmission. In addition, the high percentage of antibiotic resistance, especially in monophasic S.Tm, limits treatment options when needed. Better S.Tm control would therefore be of benefit both for farm animals and for safety of the human food chain. A promising pre-harvest intervention is vaccination. In this study we tested safety and immunogenicity of an oral inactivated S.Tm vaccine, which has been recently shown to generate an "evolutionary trap" and to massively reduce S.Tm colonization and transmission in mice. We show that this vaccine is highly immunogenic and safe in post-weaning pigs and that administration of a single oral dose results in a strong and long-lasting serum IgG response. This has several advantages over existing - mainly live - vaccines against S.Tm, both in improved seroconversion and reduced risk of vaccine-strain persistence and reversion to virulence.

BACKGROUND: Dengue fever is an important public health problem, especially in Asia and South America. A tetravalent live attenuated dengue vaccine was manufactured in India after receipt of vaccine strains from NIAID, NIH, USA. METHODS: This was a Phase 1, double-blind, randomized, placebo-controlled study performed in 60 healthy adults of 18 to 45 years. Participants were randomized 2:1 to receive a single subcutaneous injection of either a tetravalent live attenuated dengue vaccine or placebo. Safety was assessed by unsolicited adverse events (AEs) and solicited reactions through 21 days after vaccination and serious adverse events (SAEs) through the entire study period of 180 days. Dengue viremia was assessed at baseline and on day 9, 11 and 13 post-vaccination using a plaque assay. Immunogenicity was assessed using the plaque reduction neutralization test (PRNT) assay using vaccine-matched wild virus serotypes (DENV 1, DENV 2, DENV 3 and DENV 4) at baseline and on 56-, 84- and 180-days post-vaccination. PRNT assay using circulating wild type DENV 1, DENV 2, DENV 3 and DENV 4 were done on day 1 and day 85 for a subset of 31 participants. RESULTS: 60 participants were randomized to receive dengue vaccine (n = 40) or placebo (n = 20). 23 participants (59 %) showed DENV vaccine viremia post- vaccination for any of the four serotypes with majority on day 9 and day 11. At baseline, all participants were naïve by dengue PRNT50 for all four serotypes in both the study groups except for four in the dengue vaccine group and two in the placebo group. On day 57, the GMTs of neutralizing antibodies ranged from 66.76 (95 % CI 36.63, 121.69) to 293.84 (95 % CI 192.25, 449.11) for all four serotypes in the dengue vaccine group. On day 181 though the titers declined, they still remained much higher than the baseline. The titers in the placebo group did not change after vaccination. Seroconversion through day 85 ranged from 79.5 % for DENV 1 to 100 % for DENV2 while in the placebo group, no participant showed seroconversion through day 85. Similar trends were noted when PRNT was done using wild DENV serotypes in both vaccine and placebo groups. Among solicited reactions, injection site erythema, rash, headache, fatigue, myalgia and arthralgia were reported more frequently in the vaccine group than placebo group. All solicited reactions were of grade 1 or grade 2 severity and completely resolved. One unrelated serious adverse event was reported in the vaccine group. CONCLUSION: A single dose of dengue vaccine was safe and well tolerated in adults. The vaccine was highly immunogenic with trivalent or tetravalent seroconversion and seropositivity in most of the participants. The study was funded by Serum Institute of India Pvt. Ltd., Pune, India. CLINICALTRIALS: gov: NCT04035278.

There is a major unmet need for strategies to improve the immunogenicity and effectiveness of pandemic influenza vaccines, particularly in poor responder populations such as neonates. Recombinant protein approaches to pandemic influenza offer advantages over more traditional inactivated virus approaches, as they are free of problems such as egg adaptation or need for high level biosecurity containment for manufacture. However, a weakness of recombinant proteins is their low immunogenicity. We asked whether the use of an inulin polysaccharide adjuvant (Advax) alone or combined with a TLR9 agonist (CpG55.2) would enhance the immunogenicity and protection of a recombinant hemagglutinin vaccine against H7N9 influenza (rH7HA), including in neonatal mice. Advax adjuvant induced predominantly IgG1 responses against H7HA, whereas Advax-CpG55.2 adjuvant also induced IgG2a, IgG2b and IgG3 responses, consistent with the TLR9 agonist component inducing a Th1 bias. Advax-CpG55.2 adjuvanted rH7HA induced high serum neutralizing antibody titers in adult mice. In newborns it similarly overcame immune hypo-responsiveness and enhanced serum anti-rH7HA IgG levels in 7-day-old BALB/C and C57BL/6 mice. Immunized adult mice were protected against a lethal H7N9 virus challenge. When formulated with Advax-CpG55.2 adjuvant, greater protection was seen with rH7HA than with inactivated H7 whole virus antigen. Advax-CpG55.2 adjuvanted rH7HA represents a promising influenza vaccine platform for further development.

OBJECTIVE: People with autoimmune disease have worse COVID-19 infection-related outcomes, lower antibody responses to COVID-19 vaccine, and higher rates of breakthrough infection. Immunosuppressive medications used to treat rheumatoid arthritis (RA) are associated with lower COVID-19 vaccine responses, though independent contributions of comorbidities, T-cell immunity, and age are less clear. We sought to test the hypothesis that RA, immunosuppressive medications used to treat RA, and older age, contribute to reduced B and T cell response to COVID-19 vaccine. METHODS: We evaluated serum samples, taken the day of 1st vaccine dose, the day of 2nd dose, 2-6 weeks after 2nd dose, 7-12 weeks after 2nd dose, 13-24 weeks after 2nd dose, and 2-6 weeks after the 3rd dose, for anti-spike IgG and neutralizing antibody levels to Wuhan and Omicron BA.1 and peripheral blood mononuclear cells (PBMC) for spike-specific IFN-γ and IL-2 production by ELISPOT assay in 46 RA and 101 non-autoimmune control participants before and after the primary series COVID-19 mRNA vaccination. RESULTS: RA participants had lower spike-specific IgG and Wuhan-strain neutralizing antibody levels 2-6 weeks compared to controls after the second dose of primary vaccine series. Neutralizing antibody levels against Omicron BA.1 were low in both groups. IFN-γ production correlated with Wuhan neutralizing antibody levels, while older age negatively correlated with spike-specific IL-2, IFN-γ and IgG. Lower antibody levels were associated with older age, RA status, and medication usage, while lower T cell responses were associated primarily with older age. CONCLUSIONS: These data indicate lower COVID-19 mRNA vaccine-induced antibody levels in persons with RA compared to individuals without RA, likely partially attributable to immune suppressive medications. At the same time, older age is associated with lower antibody and cellular immune response to COVID-19 vaccines.

OBJECTIVE: This systemic review aimed to evaluate the effectiveness of interventions for increasing the uptake of immunisation in healthcare workers (HCWs) compared to no or alternative interventions. METHODS: A systematic review was undertaken (until March 2022) using a search strategy established a priori to capture studies that examined the effect of interventions on vaccination levels in HCWs. We included randomised controlled trials (RCT), cluster RCTs, controlled before-after (CBA) studies and interrupted time-series (ITS) studies. We described studies descriptively and synthesized results with a fixed-effect or random-effects model meta-analysis, where appropriate. The risk of bias was assessed for each study; the quality evidence per comparison was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We identified three RCTs, six cluster RCTs and four ITS studies. There was a diverse range of interventions; many included an educational component. Based on the evidence examined the following may be effective strategies in increasing the proportion of HCWs vaccinated: policy interventions, targeted and multicomponent strategies, tailored programs directed at management, physician delivered education with a vaccine 'champion' and individual decision analysis. Limited eligible studies restricted synthesis and interpretation of findings. No studies evaluated the effectiveness of legislation. Nor did we find studies evaluating the effectiveness of incentives on their own or studies focusing solely on improving access to vaccination. We judged all the studies as either unclear or high risk of bias. CONCLUSION: Few robust studies that evaluate interventions to increase vaccination in HCWs are available. A limitation of this systematic review is that interventions are diverse, poorly reported and few were sufficiently alike to combine in an evaluation. More research on the effects of interventions to increase vaccination in HCWs is required, this should address a variety of vaccines and not just influenza vaccination.

BACKGROUND: DS-5670a is a vaccine candidate for coronavirus disease 2019 (COVID-19) harnessing a novel modality composed of messenger ribonucleic acid (mRNA) encoding the receptor-binding domain (RBD) from the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encapsulated in lipid nanoparticles. Here, we report the safety, immunogenicity, and pharmacokinetic profile of DS-5670a from a phase 2 clinical trial in healthy adults who were immunologically naïve to SARS-CoV-2. METHODS: The study consisted of an open-label, uncontrolled, dose-escalation part and a double-blind, randomized, uncontrolled, 2-arm, parallel-group part. A total of 80 Japanese participants were assigned to receive intramuscular DS-5670a, containing either 30 or 60 µg of mRNA, as two injections administered 4 weeks apart. Safety was assessed by characterization of treatment-emergent adverse events (TEAEs). Immunogenicity was assessed by neutralization titers against SARS-CoV-2, anti-RBD immunoglobulin (Ig)G levels, and SARS-CoV-2 spike-specific T cell responses. Plasma pharmacokinetic parameters of DS-5670a were also evaluated. RESULTS: Most solicited TEAEs were mild or moderate with both the 30 and 60 µg mRNA doses. Four participants (10 %) in the 60 µg mRNA group developed severe redness at the injection site, but all cases resolved without treatment. There were no serious TEAEs and no TEAEs leading to discontinuation. Humoral immune responses in both dose groups were greater than those observed in human convalescent serum; the 60 µg mRNA dose produced better responses. Neutralization titers were found to be correlated with anti-RBD IgG levels (specifically IgG1). DS-5670a elicited antigen-specific T helper 1-polarized cellular immune responses. CONCLUSIONS: The novel mRNA-based vaccine candidate DS-5670a provided favorable immune responses against SARS-CoV-2 with a clinically acceptable safety profile. Confirmatory trials are currently ongoing to evaluate the safety and immunogenicity of DS-5670a as the primary vaccine and to assess the immunogenicity when administered as a heterologous or homologous booster. TRIAL REGISTRY: https://jrct.niph.go.jp/latest-detail/jRCT2071210086.

SpikoGen® is a recombinant spike protein vaccine against COVID-19 that obtained marketing authorization in the Middle East on October 6th, 2021, becoming the first adjuvanted protein-based COVID-19 vaccine of its type to achieve approval. SpikoGen® vaccine utilizes a unique adjuvant Advax-CpG55.2, which comprises delta inulin and CpG55.2 oligonucleotide, a synthetic human toll-like receptor (TLR)-9 agonist. As part of a safety assessment, developmental and reproductive toxicity (DART) studies were undertaken in mice of Advax-CpG55.2 adjuvanted formulations including SpikoGen®, a H7 hemagglutinin influenza vaccine (rH7HA), the bivalent combination of SpikoGen® and rH7HA, and a next-generation quadrivalent spike protein vaccine. In the first study, vaccines were administered intramuscularly to pregnant dams on gestation days (GD) 6.5 and 12.5, and in the second two doses were given in the pre-mating period with a further two doses during gestation. The doses used in the pregnant mice were 250-1000 times the usual human doses on a weight for weight basis. Strong serum antibody responses with neutralizing activity against the relevant virus were seen in the immunized dams and also at the time of weaning in the sera of their pups, consistent with robust maternal antibody transfer. No adverse effects of any of the vaccine formulations were observed in the immunized dams or their pups. Notably, there were no adverse effects of any of the Advax-CpG55.2 adjuvanted vaccines on female mating performance, fertility, ovarian or uterine parameters, embryo-fetal or postnatal survival, fetal growth, or neurofunctional development. No evidence of antigen interference was observed when SpikoGen® vaccine was mixed and co-administered with influenza hemagglutinin vaccine to pregnant dams. Together with the strong safety profile of SpikoGen® vaccine seen in adults and children in human trials, this DART study data supports the safety of Advax-CpG55.2 adjuvanted COVID-19 and influenza vaccine in women of childbearing potential including during pregnancy.

BACKGROUND: Vaccines are urgently required to control Staphylococcus aureus hospital and community infections and reduce the use of antibiotics. Here, we report the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in patients undergoing elective surgery for closed fractures. METHODS: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial was carried out in 10 clinical research centers in China. Patients undergoing elective surgery for closed fractures, aged 18-70 years, were randomly allocated at a ratio of 1:1 to receive the rFSAV or placebo at a regimen of two doses on day 0 and another dose on day 7. All participants and investigators remained blinded during the study period. The safety endpoint was the incidence of adverse events within 180 days. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as opsonophagocytic antibodies. RESULTS: A total of 348 eligible participants were randomized to the rFSAV (n = 174) and placebo (n = 174) groups. No grade 3 local adverse events occurred. There was no significant difference in the incidence of overall systemic adverse events between the experimental (40.24 %) and control groups (33.72 %) within 180 days after the first immunization. The antigen-specific binding antibodies started to increase at days 7 and reached their peaks at 10-14 days after the first immunization. The rapid and potent opsonophagocytic antibodies were also substantially above the background levels. CONCLUSIONS: rFSAV is safe and well-tolerated in patients undergoing elective surgery for closed fractures. It elicited rapid and robust specific humoral immune responses using the perioperative immunization procedure. These results provide evidence for further clinical trials to confirm the vaccine efficacy. China's Drug Clinical Trials Registration and Information Publicity Platform registration number: CTR20181788. WHO International Clinical Trial Registry Platform identifier: ChiCTR2200066259.

SARS-CoV-2 vaccination has been reported to be associated with the induction of thyroid disorders. To investigate the influence of SARS-CoV-2 vaccination on the disease course of patients who were undergoing treatment for Graves' disease (GD), a total of 651 consecutive GD patients who attended follow-up visits in Jiangyuan Hospital were enrolled in this retrospective study, including 443 inactivated SARS-CoV-2 vaccine recipients and 208 unvaccinated participants. The changes in serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and TSH receptor antibody (TRAb) were analyzed. Crude and adjusted hazard ratios (HRs) were estimated using Cox regression models to investigate the risks in incident TRAb positivity and hyperthyroidism recurrence following vaccination. The median levels of TRAb and fT3 significantly decreased in both vaccinated and unvaccinated groups during the GD hyperthyroidism treatment. The fT4 levels of both groups were well within normal limits and presented downward trends simultaneously. Although the present study observed an increasing trend of TSH level during follow-up, significant difference was not seen in both vaccinated and unvaccinated groups. Except for newly diagnosed GD patients, vaccinated participants had significantly lower risks of incident TRAb positivity (adjusted HR = 0.22; 95%CI: 0.10-0.48, P < 0.001) after adjusted for sex, age, disease duration and MMI dose at baseline. Besides, vaccination was unlikely to serve as a risk factor for hyperthyroidism recurrence (adjusted HR = 1.20; 95%CI: 0.51-2.83, P = 0.678). Notably, newly diagnosed patients who received vaccination were just as likely to achieve remission of thyrotoxicosis as those not receiving the vaccination at any time. Our results concluded that inactivated SARS-CoV-2 vaccination would not disturb the treatment course among GD hyperthyroidism patients.

In October/December 2021, World Health Organization and other international agencies recommended the offer of the third dose of anti-SARS-CoV-2 vaccine. In this period, the routine offer of seasonal influenza vaccination was also guaranteed and simultaneous administration of the two vaccines was encouraged. This study aims to evaluate the safety profile and to estimate the incidence of SARS-CoV-2 breakthrough infections in subjects receiving the anti-SARS-CoV-2 and influenza vaccines simultaneously. The study population was represented by healthcare workers (HCWs) of Bari Policlinico General Hospital who received the influenza (Flucelvax Tetra®) and/or anti-SARS-CoV-2 vaccination (BNT162b2 mRNA COVID-19 vaccine, Comirnaty®) either in coadministration or separately in October 2021. Reports of adverse events following immunization (AEFIs) were investigated to study the safety of both vaccines in coadministration and in separate-instance administration. Post-vaccination SARS-CoV-2 breakthrough infection was also studied. 942 HCWs accepted to join our study. 610/942 received both vaccines simultaneously. 25.26 % subjects (238/942) were only vaccinated against SARS-CoV-2, while the remaining 94 HCWs received the influenza vaccination first and subsequently received the anti-SARS-CoV2 booster dose. 717 HCWs reported AEFIs (Reporting Rate 76.1 per 100 subjects). Simultaneous administration of the two vaccines was not related with an increase of the rate of AEFIs compared to the single administration of SARS-CoV-2 vaccine, but the AEFIs' rate was lower among subjects who received only influenza vaccine. Post-vaccination SARS-CoV-2 infections were notified for 41.5 % of enrolled subjects (391/942). Incidence of breakthrough infection and symptomatic disease was not significantly different between the simultaneous administration group and other subjects. Our data suggests that simultaneous administration of a quadrivalent influenza vaccine and an mRNA anti-SARS-CoV-2 vaccine neither affected the safety of said products nor was associated with a higher risk of SARS-CoV-2 breakthrough infection.

BACKGROUND: There is limited data directly comparing the effectiveness of different COVID-19 vaccines. METHODS: We compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics. RESULTS: As a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). CONCLUSIONS: Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.

BACKGROUND: Cameroon has been struggling with low Covid-19 vaccination coverage, with only 4.5 % of the population receiving the primary series as of November 2022. The COVID-19 Vaccine Delivery Partnership (CoVDP) conducted a high-level mission to Cameroon to assess progress and advocate for actions to address bottlenecks. The objective of the mission was to administer at least 3,000,000 doses of vaccines during the 5th Mass vaccination campaign. This study examines the factors contributing to the success of the campaign and uses a geographical and gender lens to assess the results. METHODS: The study is a secondary analysis of data from the DHIS2 collected during the 5th mass vaccination campaign for Covid-19. Descriptive statistics were used to assess coverages per location and gender expressed in OR. sccess factors, and chi-squared tests were used to assess differences in vaccine distribution across regions and by gender. RESULTS: This 5th vaccination campaign benefitted from a strong political commitment facilitated by CoVDP's mission, international support, collaboration, planning, supervision, and demand generation. The campaign recorded 2 019 118 administered vaccine doses, a staggering 46-fold increase in vaccinated individuals relative to the first round, with vaccination coverage reaching 10.1 % of the general population. However, the study reveals regional and gender disparities in vaccination coverage. Men had higher odds of being vaccinated than women in the three Sahel regions. Among individuals with comorbidities, the national coverage rate was only 14 %, and the Far North and East regions exhibited the lowest coverage rates. Janssen was the most used vaccine, and the total AEFI cases reported were 2 per 1000 vaccine doses. CONCLUSION: The 5th COVID-19 vaccination campaign in Cameroon saw a strong political commitment and was the most successful so far. Despite the gains, there was gender disparity in coverage in some regions. It is important to continue the established momentum, ensure equitable access in the Sahel regions, and reach high-priority groups with primary series and booster doses.

For the batch release of vaccines, potency release assays are required. Non-animal in vitro tests have numerous advantages and are preferred; however, several vaccines are still released using in vivo assays. Their major drawback is the inherent variability with its practical implications. We quantified the variability of in vivo potency release assays for whole-cell pertussis, inactivated polio and meningococcal B (MenB) vaccines which showed large CV (Coefficient of Variation) ranging from 34% to 125%. As inherent variability might potentially be attributed to the highly variable immune system between individual animals, we evaluated the antibody titres to four MenB antigens in 344 individual outbred mice. These varied strongly, with more than 100-fold differences in antibody titres in responsive mice. Furthermore, within individual mice there was generally no correlation between the strengths of the responses to the four antigens. A mouse with a very low or no response to one antigen in many cases exhibited a strong response to another antigen. The large differences between individual animals is likely a considerable contributor to the inherent variability of in vivo potency assays. Our data again support the notion that it is preferred to move away from in vivo potency assays for monitoring batch to batch consistency as part of vaccine batch release testing.

BACKGROUND: Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines. METHODS: We collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated. RESULTS: Among 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes. CONCLUSIONS: Vaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.

INTRODUCTION: Human Papilloma Virus (HPV) is responsible for the development of cervical, vaginal, vulvar, penile, oropharyngeal and anal cancers. Throughout the UK, Immunisation nurses (IMNs) deliver school-based HPV vaccinations to students 12-13 years old. Providing HPV education to 15-17 year old students may promote decision-making regarding their sexual health and award opportunity for unvaccinated students to self-consent to the vaccination. This study aims to explore the perceptions of IMNs regarding the value of providing HPV education to 15-17 year old students and to explore whether IMNs feel that the design/delivery of this education should form part of their professional role. METHODS: Six focus groups were conducted online with IMNs from all five Health and Social Care Trusts in Northern Ireland, UK, between January-June 2021. Data were analysed using the COM-B model to identify factors that might influence IMNs' behaviour towards designing/delivering this education for 15-17 year old students. RESULTS: IMNs were highly motivated to design and deliver this HPV education. Facilitators promoting this behaviour included their specialist training, their previous sexual health teaching experience and their desire to educate young people. Barriers negatively influencing this behaviour included lack of time/resources, parental influences, lack of school support and lack of teaching/presentation skills training. CONCLUSION: IMNs feel that they are the most appropriate professionals to design/deliver HPV education for 15-17 year old students. National policy change, based on collaboration between the Public Health Agency and Education Authority, is a key factor in facilitating IMNs to implement this school-based HPV education intervention.

The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted. This adult cohort of 298 participants, oversampled for at-risk populations, was composed of 29% Māori and 28% Pacific peoples, with 40% of the population aged 55+. A significant proportion of the cohort was obese and presented with at least one comorbidity. Sera were collected 28 days and 6 months post second vaccination and 28 days post third vaccination. SARS-CoV-2 anti-S IgG titres and neutralising capacity using surrogate viral neutralisation assays against variants of concern, including Omicron BA.1, were investigated. The incidence of SARS-CoV-2 infection, within our cohort, prior to third vaccination was very low (<6%). This study found a third vaccine significantly increased the mean SARS-CoV-2 anti-S IgG titres, for every demographic subgroup, by a minimum of 1.5-fold compared to titres after two doses. Diabetic participants experienced a greater increase (∼4-fold) in antibody titres after their third vaccination, compared to non-diabetics (increase of ∼ 2-fold). This corrected for the deficiency in antibody titres within diabetic participants which was observed following two doses. A third dose also induced a neutralising response against Omicron variant BA.1, which was absent after two doses. This neutralising response improved regardless of age, BMI, ethnicity, or diabetes status. Participants aged ≥75 years consistently had the lowest SARS-CoV-2 anti-S IgG titres at each timepoint, however experienced the greatest improvement after three doses compared to younger participants. This study shows that in the absence of prior SARS-CoV-2 infection, a third Pfizer-BioNTech BNT162b2 vaccine enhances immunogenicity, including against Omicron BA.1, in a cohort representative of at-risk groups in the adult New Zealand population.

OBJECTIVE: Countries routinely offering acellular pertussis vaccine, where long-term protection is not sustained, have the challenge of selecting an optimal schedule to minimise disease among young infants. We conducted a narrative systematic review and synthesis of information to evaluate different pertussis immunisation strategies at controlling pertussis disease, hospitalisation, deaths, and vaccine effectiveness among young infants. METHODS: We conducted a review of the literature on studies about the primary, booster, and/or maternal vaccination series and synthesised findings narratively. Countries offering the first three doses of vaccine within six-months of life and a booster on or before the second year or life were defined as accelerated primary and booster schedules, respectively. Countries offering primary and booster doses later were defined as extended primary and booster schedules. All search results were screened, and articles reviewed and reconciled, by two authors. The Risk of Bias in Non-randomised Studies of Intervention tool was used to evaluate the risk of bias. FINDINGS: A total of 98 studies were included in the analyses and the following recurring themes were described: timing of vaccination, vaccine coverage, waning immunity/vaccine effectiveness, direct and indirect effectiveness, switching from an accelerated to extended schedule, impact of changes in testing. The risk of bias was generally low to moderate for most studies. CONCLUSION: Comparing schedules is challenging and there was insufficient evidence to that one schedule was superior to another. Countries must select a schedule that maintains high vaccine coverage and reduced the risk of delaying the delivery vaccines to protect infants.

The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs). Canada's National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance. In this paper, we describe: structural adaptations in response to the accelerated pace and amount of work required to issue recommendations that were timed around product authorizations and dynamic epidemiology; technical adaptations in response to rapidly evolving evidence of variable quality which required close monitoring, and which promoted reliance on basic vaccine principles due to incomplete direct evidence; the need to provide nimble advice (e.g., off-label recommendations, preferential recommendations); communications adaptations (e.g. identify sustainable spokespeople for the committee, receive stakeholder feedback, and ensure urgent nuanced advice was communicated to a diverse audience); and research adaptations focussing on solutions to constrained supply (e.g. prioritisation, extended intervals, and heterologous schedules). The early pandemic vaccine experience has created a roadmap of lessons and adaptations that should be leveraged in future pandemic vaccine programs, and has highlighted the essential role of NITAGs to complement regulatory structures during pandemics to ensure timely, impactful, and evidence-informed public health vaccine guidance.

BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention.

BACKGROUND: Vaccination rates worldwide have declined in recent years. This decrease is primarily driven by vaccine hesitancy, which remains understudied in Central Asia, including Kazakhstan. Furthermore, there is great concern about parental hesitancy toward COVID-19 vaccines, as previous studies have focused on adult vaccine hesitancy. The current study was conducted by UNICEF and funded by USAID to explore the drivers of routine and COVID-19 immunization behaviors among parents and caregivers in Kazakhstan. METHODS: Using a cross-sectional methodology, researchers conducted 3081 face-to-face interviews with parents and caregivers of children aged 0-17 years across cities and villages in Kazakhstan. A tablet-based questionnaire (CAPI) was utilized, collecting participants' data on sociodemographic characteristics, childhood and COVID-19 vaccination behaviors, and potential drivers. RESULTS: Total of 239 participants (7.8%) were found to previously refuse vaccination due to their own beliefs. Stronger belief that vaccines are efficacious (AdjOR = 0.47), stronger belief that childhood vaccines are safe and danger of vaccine-preventable diseases is high (AdjOR = 0.73), firmer trust in societal factors (AdjOR = 0.77) and positive attitudes of family members toward immunization (AdjOR = 0.6) were significantly associated with parental refusal of childhood vaccines. The large proportion of respondents (N = 2,634, 85.6%) missed the COVID-19 vaccination of their child or were unwilling to get vaccinated. Stronger belief that COVID-19 vaccines are safe and efficacious (AdjsOR = 0.18), lacking important information about COVID-19 vaccines (AdjOR = 1.25) and parents being unvaccinated against COVID-19 (AdjOR = 2.3) were significant predictors of vaccine hesitancy. CONCLUSION: This study revealed numerous socio-demographic and behavioral factors significantly associated with parental refusal of childhood vaccines and hesitancy toward COVID-19 vaccines. Many parents not refusing vaccination possessed negative attitudes towards vaccines. Potential changes in their attitudes and beliefs of parents were observed compared to findings from pre-COVID era. Continuous monitoring of parental hesitancy, proper interventions and education of healthcare workers are suggested to reduce parental vaccine hesitancy.

BACKGROUND: To combat the SARS-CoV-2 pandemic, multiple vaccines using different manufacturing platforms have been developed, including NVX-CoV2373 (an adjuvanted recombinant protein vaccine). As SARS-CoV-2 variants have emerged, some of which evade vaccine-induced immunity, introduction of vaccine booster doses has become critical. Employing different vaccine types for primary series vaccination and boosting could expand vaccine coverage and access. This study assessed whether NVX-CoV2373 would induce robust responses when used as a booster. METHODS: The 2019nCoV-307 study was a phase 3, randomized, observer-blinded trial evaluating immunogenicity and safety of NVX-CoV2373 in previously vaccinated adults aged 18-49 years in the United States (NCT05463068). Participants were randomized 1:1:1 to receive one intramuscular injection of NVX-CoV2373 from one of three different manufacturing lots. Immunogenicity was assessed by immunoglobulin G (IgG) and neutralizing antibodies (NAb). These responses were compared for the three lots, and for participants with primary series with or without a prior booster dose of the mRNA-1273, BNT162b2, Ad26.COV2.S, or NVX-CoV2373 COVID-19 vaccines. RESULTS: A total of 911 participants were randomized between July 11 and 13, 2022, with 905 being assessed for safety and 848 for immunogenicity. Immunogenicity of NVX-CoV2373 met prespecified equivalence criteria between lots, and the booster dose was well-tolerated. NVX-CoV2373 induced robust IgG and NAb responses when used as a first or later booster dose, regardless of primary series vaccine type. Seroconversion rates were also similar across previous vaccine types. Induced antibodies were strongly reactive, even to the immune-evasive Omicron BA.1 and BA.5 variants. CONCLUSIONS: NVX-CoV2373 showed consistent immunogenicity between lots, with no new safety signals identified. Use of NVX-CoV2373 as a booster dose (first or later) is supported.

Measles outbreaks have raised concerns of fatal infections in immunocompromised patients. Canadian guidelines advise administration of live vaccines, such as measles, mumps, and rubella (MMR), two yearsafter hematopoietic stem cell transplant (HSCT) yet studies have not assessed eligibility based on medication contraindications. We retrospectively reviewed the charts of 72 autologous (auto-HSCT) and 68 allogeneic (allo-HSCT) recipients at the Windsor Regional Cancer Center to determine MMR reactivity and eligibility based on administration of contraindicated medications two years post-HSCT. Reactivity to measles, mumps, and rubella in auto-HSCT recipients was 49.1 %, 28.8 %, and 52.3 %, respectively, and in allo-HSCT recipients was 75.6 %, 57.8 %, and 64.4 %, respectively. Immunity to all three components was significantly different between transplant types (p = 0.0002). Nearly 80 % of auto-HSCT patients were on a contraindicated medication at two years compared to 45 % of allo-HSCT recipients. Auto-HSCT recipients require MMR revaccination, but it is contraindicated in a large proportion of patients.

The COVID-19 pandemic has posed an unprecedented impact on Americans for over three years. To control the damage, a booster shot becomes increasingly necessary because the efficacy of the initial vaccine is waning and new variants of the virus are emerging. This study aims to understand factors at both individual and state levels that influence one's decision to take the monovalent booster. We merged data from a national survey administered in the Spring of 2022 with state-level indicators of the political climate, income inequality, and public health conditions. Multilevel logistic regression is adopted for statistical estimation. Findings show contrasting effects of the social network. More vaccinated people in one's network promote booster uptake, while more family members and close friends who contracted the virus in one's network inhibit booster uptake. In addition, residents of states with more votes for the Democratic candidate in the 2020 general election are more likely to take the booster. Meanwhile, residents from states with high income inequality are less likely to become boosted. This study identified multilevel determinants of the individual decision to receive the monovalent COVID-19 booster. The results imply the need to leverage the social network, weaken partisanship salience, and reduce income inequality to encourage booster uptake.

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection that is mainly caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16). As there are no specific therapeutics for HFMD, the development of a bivalent vaccine is required to cover a broad range of infections. In this study, the effectiveness of novel monovalent and bivalent vaccines targeting EV71 C4a and CVA16 was investigated for their ability to prevent viral infections in neonatal human scavenger receptor class B member 2 (hSCARB2) transgenic mice. As hSCARB2 serves as a key viral receptor for EV71, these transgenic mice are susceptible to EV71 strains and facilitate viral binding, internalization, and uncoating processes. Antisera prepared by vaccine immunization were transferred to 2-day-old hSCARB2 transgenic mice, which were then infected with EV71 C4a or CVA16 virus. The antisera generated by each monovalent or bivalent vaccine effectively protected against EV71 C4a and CVA16 infections. The examination of tissue damage and viral contents in various organs indicated that both monovalent and bivalent antisera reduced EV71 C4a viral load in the brainstem, and no significant tissue damage was observed. During CVA16 infection, the monovalent and bivalent antisera significantly reduced viral contents in both the brainstem and muscles. These results suggest that passive immunity by monovalent and bivalent antisera can effectively protect against EV71 C4a and CVA16 infections. Thus, the development of a bivalent vaccine that can provide broad protection against both CV and EV infections may be a promising strategy in preventing HFMD.

INTRODUCTION: The incidence of invasive meningococcal disease (IMD) among Norwegian 16-19-year-olds was 1-7/100,000 in the decade before the COVID-19 pandemic, with serogroup Y (MenY) dominance. In contrast to many other European countries, meningococcal vaccines are not part of the national immunisation program (NIP) in Norway. This cross-sectional study aimed to measure the degree of natural immunity against Neisseria meningitidis among adolescents in Norway to evaluate the need for introducing tetravalent meningococcal conjugate vaccine (MCV4) in the NIP. MATERIALS AND METHODS: Serum and saliva samples were collected from students in upper and lower secondary schools in Norway in 2018. Samples were analysed for meningococcal capsular polysaccharide (PS)-specific antibodies using a bead-based multiplex immunoassay. PS-specific antibody levels were linked to data on meningococcal carriage, vaccination status and risk factors for carriage (assessed with questionnaire) and analysed by linear regression of log transformed concentrations. A subset of samples from unvaccinated individuals was analysed for serum bactericidal antibodies (SBA). RESULTS: A total of 1344 participants, median age 16 years (range 12-24), were included in the study. Overall, 60.9% of the participants were female and 1137 (84.6%) were not vaccinated with MCV4. PS-specific antibody concentrations in serum and saliva were low among unvaccinated individuals for all serogroups and only 6.7-20.0% of the subpopulation with high PS-specific antibodies assessed with SBA had protective levels. Unvaccinated MenY carriers had higher levels of MenY anti-PS IgG in serum and IgA in saliva than those not carrying MenY. Use of Swedish snus was associated with lower anti-PS IgG levels in serum and waterpipe use with lower anti-PS IgG levels in saliva. CONCLUSION: Unvaccinated adolescents in Norway have a low degree of natural immunity against the serogroups of N. meningitidis predominating among cases of IMD in this age group. Therefore, introduction of MCV4 for adolescents in the NIP is recommended.

The high-density microprojection array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. HD-MAPs provide an alternative to needle and syringe (N&S) vaccination. Additional advantages could include reduced cold-chain requirements, reduced vaccine dose, reduced vaccine wastage, an alternative for needle phobic patients and elimination of needlestick injuries. The drivers and potential benefits of vaccination by self-administering HD-MAPs are high patient acceptance and preference, higher vaccination rates, speed of roll-out, cost-savings, and reduced sharps and environmental waste. The HD-MAP presents a unique approach in pandemic preparedness and routine vaccination of adults. It could alleviate strain on the healthcare workforce and allows vaccine administration by minimally-trained workers, guardian or subjects themselves. Self-vaccination using HD-MAPs could occur in vaccination hubs with supervision, at home after purchasing at the pharmacy, or direct distribution to in-home settings. As a result, it has the potential to increase vaccine coverage and expand the reach of vaccines, while also reducing labor costs associated with vaccination. Key challenges remain around shifting the paradigm from medical professionals administrating vaccines using N&S to a future of self-administration using HD-MAPs. Greater awareness of HD-MAP technology and improving our understanding of the implementation processes required for adopting this technology, are critical factors underpinning HD-MAP uptake by the public.

The highest death toll during the COVID-19 pandemic in Thailand was among unvaccinated older adults. Deaths among older adults in Narathiwat Province were related to a lower COVID-19 vaccination rate. This study explored the factors influencing COVID-19 vaccination hesitancy in a Muslim community with low vaccination rates. A case-control study was conducted with participants assigned to the unvaccinated "case" group and the vaccinated "control" group. The sample was Thai older adults who practiced Islam and lived in Narathiwat Province. Purposive sampling was conducted by selecting a case house and finding the control around the case house in a 1:2 ratio. This study included 141 participants with a median age of 67 years (interquartile range [IQR], 8). More than 80% of both groups were retired and lived with their extended relatives. More participants in the vaccinated group believed that vaccines could prevent death from COVID-19 than in the unvaccinated group. In the multivariable analysis, factors related to the low perceived importance of the COVID-19 vaccination (odds ratio [OR] = 2.63) and a lack of vaccine recommendation from religious leaders (OR = 4.67) significantly influenced COVID-19 vaccination refusal. The COVID-19 guidance from religious leaders and the perceived importance of COVID-19 vaccination influence vaccination uptake among Muslim older adults in Thailand.

BACKGROUND: Mumps is still endemic in Japan because mumps vaccination is voluntary. In this study, we investigated associations of parental socioeconomic status, family structure, and knowledge/belief about mumps and mumps vaccine with parental decision to vaccinate their children. We also evaluated effectiveness of a campaign based on survey results. METHODS: We conducted a cross-sectional survey of parents with children aged 1-6 years attending preschools or kindergartens in Tokamachi City, Japan. We assessed the association of parental factors with their decision to vaccinate their children using multivariable logistic regression analyses. We designed a campaign based on the survey results, and compared the number of annual vaccinations at Tokamachi Hospital per the child population aged 1-6 years in Tokamachi City before and after the campaign using a trend test. RESULTS: In total, 1391 of 1617 (86%) eligible parents completed the survey. Among these parents, 229 (16%) vaccinated their children. In multivariable analyses, higher parental education [odds ratio (OR) = 2.21; 95% CI, 1.59-3.08; P < 0.001], greater knowledge about mumps and the mumps vaccine (OR = 1.88; 95% CI, 1.60-2.21; P < 0.001), and living without grandparents (OR = 1.44; 95% CI, 1.05-1.99; P = 0.024) were significantly associated with parental decision to vaccinate their children. The number of annual vaccinations per the child population significantly increased following the campaign (P < 0.001). CONCLUSION: Our study showed several sociodemographic factors significantly associated with mumps vaccination. Further research is needed to examine the relevance of our findings to the uptake of other voluntary vaccines among children.

The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to investigate the immunogenicity of an aluminum hydroxide (Alum) and CpG adjuvanted inactivated vaccine (IAV) candidate against SARS-CoV-2 in mice. A comparison was made between the immune response of mice vaccinated with the Alum+CpG adjuvant IAV and those vaccinated with the Alum adjuvant IAV. Mice immunized with Alum+CpG adjuvant IAV demonstrated high antibody titers and a durable humoral immune response, as well as a Th1-type cellular immune response. Notably, compared to Alum alone vaccine, the Alum+CpG adjuvant IAV induced significantly higher proportions of GC B cells in the splenocytes of immunized mice. Importantly, the changes in inflammatory cytokine levels in the sera of mice vaccinated with the Alum+CpG adjuvant IAV followed a similar trend to that of the Alum adjuvant IAV, which had been proven safe in clinical trials. Overall, our results demonstrate that Alum+CpG adjuvant has the potential to serve as a novel adjuvant, thereby providing valuable insights into the development of vaccine formulations.

Canine vaccine hesitancy (CVH) can be thought about as dog owners' skepticism about the safety and efficacy of administering routine vaccinations to their dogs. CVH is problematic not only because it may inspire vaccine refusal - which may in turn facilitate infectious disease spread in both canine and human populations - but because it may contribute to veterinary care provider mental/physical health risks. In a nationally representative survey of US adults (N = 2200), we introduce a novel survey-based instrument for measuring CVH. We document pervasive CVH in dog owner subpopulations. Troublingly, we find that CVH is associated with rabies non-vaccination, as well as opposition to evidence-based vaccine policies. We conclude by discussing the human and animal health consequences of CVH, and outline a research agenda for future opinion-based research on this important topic.

INTRODUCTION: Shoulder Injury Related to Vaccine Administration (SIRVA) is a rare disorder characterized by persistent shoulder pain and limited range of motion presenting within 48 h after vaccine administration. With the widespread distribution of the COVID-19 vaccine, the incidence of SIRVA is expected to rise. This sudden rise in vaccine administration presents an ideal opportunity to estimate the prevalence of SIRVA and to better characterize SIRVA. OBJECTIVE: This study aims to investigate the prevalence of SIRVA following COVID-19 vaccine administration among hospital workers in the Netherlands. METHODS: A questionnaire was sent to all hospital workers from a single non-academic hospital in the Netherlands. Respondents who had active SIRVA complaints were invited for an outpatient orthopaedic clinic assessment. Data was collected on participant characteristics and physical examination including assessment of active and passive range of motion (ROM). An ultrasound was performed to identify potential abnormalities. RESULTS: 32 out of 981 (3.3%) respondents reported shoulder pain with limited ROM occurring within 48 h after vaccine administration lasting for at least 7 days. Of these 32 respondents with SIRVA, 18 (56.2%) still reported active symptoms at the time of the survey. Clinical examination of 13 (72.2%) respondents with active SIRVA complaints showed limited glenohumeral ROM, limitations in activities of daily living and injection site pain. Twelve out of thirteen (92.3%) respondents with active SIRVA complaints showed abnormalities of the soft-tissue of the shoulder on ultrasound. Physiotherapy was the most common treatment modality for persistent SIRVA complaints (38.9%). CONCLUSIONS: The prevalence of SIRVA is estimated at 3% in the adult working population. Signs and symptoms of SIRVA are variable in severity, localization and timing. Soft-tissue abnormalities is the most common clinical sign. This study contributes to clinician's knowledge on SIRVA, aiding in early recognition and treatment, which are imperative for prevention of persistent and severe shoulder pathology.

Atypical hemolytic uremic syndrome is a rare, life-threatening disorder which can be triggered by COVID 19 infection and COVID 19 vaccination then induce multiple organ failure. Our study is the first to evaluate immune responses to COVID-19 vaccination and safety in a cohort of patients in a local single-center study in Taiwan.. Results indicate that vaccines effectively shield aHUS patients from severe COVID-19 complications without significant safety concerns. A double booster dose for the third vaccine is essential for optimal efficacy. Anti-complement therapy did not influence vaccination effectiveness. Transplant aHUS patients had the lowest immune response titers, indicating a need for additional vaccine doses. Compared to healthcare workers, aHUS patients had poor T-cell responses. We noted a superior trend with mixed-type COVID-19 vaccinations in aHUS patients, while fixed-type mRNA demonstrated better results in healthcare workers. Our findings endorse COVID-19 vaccination as a potent strategy to safeguard aHUS patients from severe complications, emphasizing the importance of vigilant monitoring pre- and post-vaccination.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a glycoprotein, expressed on the virion surface, that mediates infection of host cells by directly interacting with host receptors. As such, it is a reasonable target to neutralize the infectivity of the virus. Here we found that a recombinant S protein vaccine adjuvanted with Alhydrogel or the QS-21-like adjuvant Quil-A effectively induced anti-S receptor binding domain (RBD) serum IgG and neutralizing antibody titers in the Syrian hamster model, resulting in significantly low SARS-CoV-2 replication in respiratory organs and reduced body weight loss upon virus challenge. Severe lung inflammation upon virus challenge was also strongly suppressed by vaccination. We also found that the S protein vaccine adjuvanted with Alhydrogel, Quil-A, or an AS03-like adjuvant elicited significantly higher neutralizing antibody titers in mice than did unadjuvanted vaccine. Although the neutralizing antibody titers against the variant viruses B.1.351 and B.1.617.2 declined markedly in mice immunized with wild-type S protein, the binding antibody levels against the variant S proteins were equivalent to those against wild-type S. When splenocytes from the immunized mice were re-stimulated with the S protein in vitro, the induced Th1 or Th2 cytokine levels were not significantly different upon re-stimulation with wild-type S or variant S, suggesting that the T-cell responses against the variants were the same as those against the wild-type virus. Upon Omicron XBB-challenge in hamsters, wild-type S-vaccination with Alhydrogel or AS03 reduced lung virus titers on Day 3, and the Quil-A adjuvanted group showed less body weight loss, although serum neutralizing antibody titers against XBB were barely detected in vitro. Collectively, recombinant vaccines coupled with different adjuvants may be promising modalities to combat new variant viruses by inducing various arms of the immune response.

The Covid pandemic took the world by surprise in late 2019 and the need for rapid development of vaccines became paramount. The challenge was how to accelerate standard vaccine development times as much as possible. With knowledge of the genetic code of SARsCOV2, vaccine manufacturers throughout the world have risen to the challenge and several new vaccines were rapidly developed for emergency use. In March 2020, global Regulatory Authorities met to consider how to start early clinical trials and accept rolling submissions. Before use in clinical trials or any mass vaccination campaigns, the safety of the candidate vaccine needs to be evaluated. Non-clinical toxicology studies are required as an important part of vaccine safety evaluation. The extent of the toxicology evaluation prior to the start of clinical trials depended on several factors, including: the type of the candidate vaccine as well as already available supportive information with the candidate vaccine or similar vaccine types. For vaccine candidates with pre-existing data, this would save valuable time whilst a full toxicology evaluation was completed in parallel. For vaccines with more limited data, toxicology data was required before clinical development could start. This workshop examined the nonclinical toxicology studies for new Covid vaccines from the perspectives of: Vaccine manufacturers with different vaccine technologies, managing global regulatory submissions/responses; CROs, managing the urgency of conducting and reporting studies and supporting new players in the vaccine world; and Regulatory Authorities, in supporting the review process, juggling the need for safety and quality with mounting pressure to approve vaccines.

Next generation influenza vaccines are in development and have the potential for widespread health and economic benefits. Determining the potential health and economic impact for these vaccines is needed to drive investment in bringing these vaccines to the market, and to inform which groups public health policies on influenza vaccination should target. We used a mathematical modelling approach to estimate the epidemiological impact and cost-effectiveness of next generation influenza vaccines in England and Wales. We used data from an existing fitted model, and evaluated new vaccines with different characteristics ranging from improved vaccines with increased efficacy duration and breadth of protection, to universal vaccines, defined in line with the World Health Organisation (WHO) Preferred Product Characteristics (PPC). We calculated the cost effectiveness of new vaccines in comparison to the current seasonal vaccination programme. We calculated and compared the Incremental Cost-Effectiveness Ratio and Incremental Net Monetary Benefit for each new vaccine type. All analysis was conducted in R. We show that next generation influenza vaccines may result in a 21% to 77% reduction in influenza infections, dependent on vaccine characteristics. Our economic modelling shows that using any of these next generation vaccines at 2019 coverage levels would be highly cost-effective at a willingness to pay threshold of £20,000 for a range of vaccine prices. The vaccine threshold price for the best next generation vaccines in £-2019 is £230 (95%CrI £192 - £269) per dose, but even minimally-improved influenza vaccines could be priced at £18 (95%CrI £16 - £21) per dose and still remain cost-effective. This evaluation demonstrates the promise of next generation influenza vaccines for impact on influenza epidemics, and likely cost-effectiveness profiles. We have provided evidence towards a full value of vaccines assessment which bolsters the investment case for development and roll-out of next-generation influenza vaccines.

BACKGROUND: The rate of anaphylaxis following COVID-19 vaccinations is estimated to be 2-11 cases per million doses administered. However, adrenaline is occasionally used in individuals who are later diagnosed with immunisation stress-related responses, as their initial presenting signs and symptoms can appear similar to that of anaphylaxis. This study aims to describe the clinical profile of individuals who had received adrenaline following a COVID-19 vaccine and their subsequent revaccination outcomes. METHODS: We examined notifications of cases who had received adrenaline following a COVID-19 vaccine in New South Wales, Australia. The cases were classified into Brighton Collaboration Case Definition (BCCD) for anaphylaxis, their clinical presentation, management and subsequent revaccination outcomes were compared. RESULTS: From 22 February 2021 to 30 September 2021, there were 222 cases where adrenaline was administered. Of these, 32 (14 %) fulfilled Level 1 BCCD, 59 (27%) Level 2, 2 (1%) Level 3, 97 (44%) Level 4 and 32 (14 %) Level 5. The most commonly reported symptoms were sensation of throat closure (n = 116, 52%), difficulty breathing (n = 82, 37%) and nausea (n = 55, 25 %). Of the 176 (79%) individuals who proceeded to further vaccination, 89 (51%) received the same vaccine formulation and only 14 (8%) experienced another allergic adverse event with 9 (5%) receiving adrenaline. CONCLUSION: Less than one in five individuals who received adrenaline met Level 1 BCCD criteria for anaphylaxis. Many reactions that were treated with adrenaline had little to no diagnostic certainty of anaphylaxis and in such cases repeat vaccination had a high likelihood of being tolerated. Increased awareness and education on objective signs and symptoms of anaphylaxis is required to ensure appropriate use of adrenaline.

BACKGROUND: The excessive covid-related mortality of psychiatric patients was reduced by vaccination. The vaccine uptake in patients diagnosed with different mental health disorders is, however, not fully described. AIMS: A nationwide, record-based retrospective cross-sectional study examines the effect of substance use, psychotic, affective, anxiety, and personality disorders on COVID-19 vaccination rates in August and December 2021. Further, it quantifies the effect of receiving mental healthcare on vaccine uptake. METHODS: The COVID-19 vaccine rates of mental healthcare users in August and December 2021 were examined using logistic regression models adjusted for sex and age on a sample of 7,235,690 adult inhabitants of the Czech Republic. The probability of vaccine uptake in the week following mental healthcare appointment or hospitalization on any day in the fall 2021 was compared to the general probability of getting vaccinated during that week. RESULTS: The vaccination rate in August 2021 was related to history of hospitalization due to substance use (OR = 0.71), personality (OR = 0.87), psychotic (OR = 0.92), and anxiety (OR = 1.15) disorders, while mood disorders had no effect (OR = 1.00). Compared to general population, mental healthcare users were undervaccinated in August but not in December 2021. Vaccine uptake was low in those with history of psychiatric hospitalizations but higher in those utilizing inpatient or outpatient mental healthcare recently, predominantly for affective disorders. Increased vaccine uptake was observed following utilization of mental healthcare as well as in those with repeated psychiatric hospitalizations. CONCLUSIONS: The vaccination rates of mental healthcare users relative to general population largely differ across nosological categories and during the vaccination campaign. Psychiatrists were successful in promoting vaccination against COVID-19.

OBJECTIVES: To assess vaccine coverage rates before and after implementation of a COVID-19 vaccine mandate among Health care Personnel (HCP) and demographic characteristics associated with vaccine uptake Design, Setting, and Participants: Cohort study conducted among 10,889 hospital employees followed from Dec 16, 2020 - October 31, 2021, at a large academic hospital in Philadelphia. MAIN OUTCOME AND MEASURES: Time to COVID-19 vaccination and vaccine series completion rates before and after implementation of a COVID-19 vaccine mandate based on age, gender, race/ethnicity, and level of patient contact/occupational group. RESULTS: The vaccination series completion rate was 86.0% prior to mandate announcement, and increased to 98.7% after mandate implementation. Rates before mandate announcement were highest among Asians (96.2%), Whites (94.0%), males (89.7%), employees ≥ 65 years of age (95.2%), and employees with direct patient care (physicians, 99.0%, and nurses, 93.3%). Hospital educational initiatives (including Town Halls and discussions with Black and Hispanic employees with the lowest vaccination rates) appeared to improve uptake. The largest increase in series completion after mandate announcement occurred among Blacks, those of other/multiracial backgrounds, and Hispanics (35.6%, 22.4%, and 10.8%, respectively) as well as those with some or no direct patient contact (24.5% and 18.3%, respectively). Medical or religious exemptions were approved for 64 (<0.6%) employees and 38 (<0.4%) left their positions (8 voluntary, 30 involuntary) specifically due to the COVID-19 vaccine mandate. No clinically meaningful differences by age, gender, or race/ethnicity for those who were vaccinated under the mandate versus those who left their positions were noted. CONCLUSIONS AND RELEVANCE: These results suggest that while mandates may be challenging to institutions and enforcement unpopular, they play an important role in reducing hesitancy and securing high vaccination rates among HCP, a group at high risk of COVID-19 given their employment and who can be a source of disease transmission to patients.

BACKGROUND: Norovirus (NoV) is the most common cause of diarrheal episodes globally. Issues with in vitro cultivation systems, genetic variation, and animal models have hindered vaccine development. Plant-derived virus-like particles (VLPs) may address some of these concerns because they are highly immunogenic, can be administered by different routes, and can be rapidly produced to accommodate emerging viral strains. METHODS: NoV VLPs (NoVLP) composed of the surface viral protein (VP) 1 of the GI and GII genogroups were produced in Nicotiana benthamiana using an Agrobacterium tumefaciens-based recombinant transient expression system. Leaves from infiltrated plants were harvested and NoVLPs were extracted and purified. The safety and immunogenicity of the GII.4 NoVLP, the genotype currently causing most human disease, were subsequently examined in rabbits and mice. RESULTS: Fifteen GI and GII NoVLPs were successfully expressed in N. benthamiana and were structurally similar to NoV virions, as determined by cryogenic transmission electron microscopy. The NoVLP was well-tolerated, with no local or systemic signs of toxicity in rabbits. Three intramuscular doses of the GII.4 NoVLP adjuvanted with aluminum hydroxide induced robust IgG titers, IgG-secreting cells, histo-blood group antigen blocking titers, and IFNγ-secreting T cells in mice. In addition to circulating antibodies, oral administration of the NoVLP in mice induced significant IgA levels in feces, indicative of a mucosal response. CONCLUSIONS: The plant-made NoVLP vaccine was safe and immunogenic in mice and rabbits. Multi-modal vaccination, combining oral and intramuscular administration could be considered for future clinical development to maximize systemic and mucosal immune responses.

BACKGROUND: This study aimed to evaluate the parental acceptance of Typhoid Conjugate Vaccine (TCV) and to determine the predictors of TCV vaccination status among children in an outbreak setting of extensively drug resistant (XDR) typhoid fever in Karachi, Pakistan. METHODS: A cross-sectional survey using the WHO recommended rapid vaccine coverage assessment technique was conducted. Out of 11, four union councils (UCs) in Lyari Town were randomly selected. A parent or primary caretaker from the eligible household was interviewed. Data were collected using a locally validated vaccine attitudes scale (VAS). Sum of scores was calculated for VAS. A higher score denoted negative attitudes and perceptions regarding TCV and vice versa. Multivariable logistic regression was performed to determine the predictors of TCV vaccination status. RESULTS: Based on the 14-item parental VAS, 78.0 % of the parents had a score between 0 to <40 and 22 % had a score ≥40. VAS score of <40 was significantly associated with higher odds of receiving TCV during the campaign setting (adjusted Odds Ratio (aOR): 1.30; 95 % Confidence Interval (CI): 1.02, 1.66). The odds of receiving TCV vaccination were higher among children whose parents were aware of the ongoing vaccination campaign in the area (aOR: 4.57; 95 % CI: 2.93, 7.12) and expressed willingness to get their child vaccinated against typhoid fever (aOR: 2.54; 95 % CI: 1.82, 3.55). CONCLUSION: Parental awareness of the ongoing vaccination campaign, positive perception and attitudes towards vaccine were found to be significantly associated with TCV vaccination among children. Appropriately structured pre-vaccination awareness campaigns focused on childhood vaccination targeted towards parents are necessary to improve parental awareness, attitude and behavior towards vaccination.

Leishmania spp. and Trypanosoma cruzi are parasitic kinetoplastids of great medical and epidemiological importance since they are responsible for thousands of deaths and disability-adjusted life-years annually, especially in low- and middle-income countries. Despite efforts to minimize their impact, current prevention measures have failed to fully control their spread. There are still no vaccines available. Taking into account the genetic similarity within the Class Kinetoplastida, we selected CD8+ T cell epitopes preserved among Leishmania spp. and T. cruzi to construct a multivalent and broad-spectrum chimeric polyprotein vaccine. In addition to inducing specific IgG production, immunization with the vaccine was able to significantly reduce parasite burden in the colon, liver and skin lesions from T. cruzi, L. infantum and L. mexicana challenged mice, respectively. These findings were supported by histopathological analysis, which revealed decreased inflammation in the colon, a reduced number of degenerated hepatocytes and an increased proliferation of connective tissue in the skin lesions of the corresponding T. cruzi, L. infantum and L. mexicana vaccinated and challenged mice. Collectively, our results support the protective effect of a polyprotein vaccine approach and further studies will elucidate the immune profile associated with this protection. Noteworthy, our results act as conceptual proof that a single multi-kinetoplastida vaccine can be used effectively to control different infectious etiologies, which in turn can have a profound impact on the development of a new generation of vaccines.

BACKGROUND: In August 2021, France enacted a COVID-19 certificate requirement (vaccination/recovery/test) to access specific services, with mandates for professional groups. We evaluated the impact of this incentive-coercive policy in terms of vaccine uptake equality, future vaccine intention and confidence in authorities' crisis management. METHODS: In late August 2021, a representative sample of adults (18-75 years) completed an internet-based questionnaire. We classified vaccinated participants by stated reasons for vaccination and estimated adjusted prevalence ratios (aPR) using multivariable Poisson regression. Counterfactual vaccine status assumed non-vaccination of those vaccinated for the certificate. We analysed the association of free-text testimonial themes with level of confidence in authorities. RESULTS: Among 972 participants, 85.7% were vaccinated or intended vaccination: 3.6% only for certificate/mandate, 17.7% mainly for certificate/mandate plus other reasons, and 64.4% mainly for other reasons. In the counterfactual situation, vaccine uptake would have been significantly more likely among older vs. younger participants (aPR = 1.35) and among those with moderate-high vs. low levels of confidence in authorities for COVID-19 crisis management (aPR = 2.04). In the observed situation, confidence was the only significant determinant of vaccine status (moderate-high vs. low, aPR = 1.39). Among those without genuine motivation for vaccination, professionally active persons were more likely to have ceded to the certificate requirement (aPR = 3.76). Those vaccinated only for the certificate were more likely to express future COVID-19 vaccine intention than unvaccinated persons (aPR = 6.41). Themes significantly associated with lower confidence were criticism of morality (aPR = 1.76) and poor communication by the authorities (aPR = 1.66). CONCLUSION: The incentive-coercive policy has reduced the negative association of vaccine status with younger age and low confidence in authorities, but may have reinforced isolation of professionally inactive persons. The requirement did not negatively impact future COVID-19 vaccine intention. Future vaccine-incentive policies should pay special attention to populations with low levels of confidence in authorities.

INTRODUCTION: Recombinant zoster vaccine (RZV) is recommended in the US for prevention of herpes zoster (HZ) in adults aged ≥50 years. Vaccination rates remain suboptimal for adults 50-59 years compared with adults ≥50 years overall. The objective of this study was to model changes in outcomes associated with improved RZV vaccination coverage in US adults 50-59 years. METHODS: A multicohort Markov model compared a scenario using real-world vaccination coverage for US adults 50-59 years in 2020 versus scenarios assuming higher coverage. Outcomes, based on a lifetime horizon, included HZ cases and complications avoided, quality-adjusted life-years (QALY), and costs. Model inputs included HZ epidemiology, RZV vaccine efficacy, coverage, adverse events, and costs, based on published literature and US sources. Some inputs were updated from previous models, including real-world estimates of RZV coverage, series completion, and reflecting longer-term data on waning of vaccine efficacy. The model utilized a cohort size of 42,756,488 individuals based on the 2020 US population census. RESULTS: The model projected that increasing RZV coverage in adults 50-59 years from 7.3 % to 14.6 % (to coverage for adults 60-64 years in 2020) would avoid an additional 504,468 HZ cases, 42,077 postherpetic neuralgia cases, and 56,247 cases of other HZ-associated complications. The increase in vaccine coverage would result in higher vaccination-related costs of $1,172,411,566, but the avoided HZ cases and complications would be expected to result in direct cost savings of $721,973,386 and indirect cost savings of $593,497,480 from avoided productivity loss. Overall, a gain of 5,230 discounted QALYs and cost savings of $143,059,299 from a societal perspective would be realized. CONCLUSION: Modestly higher RZV coverage in US adults 50-59 years could reduce the clinical burden associated with HZ and may result in societal cost savings. These findings demonstrate the potential value of increasing RZV vaccination in this population.

Typhoid and emerging paratyphoid fever are a severe enteric disease worldwide with high morbidity and mortality. Licensed typhoid vaccines are in the market, but no paratyphoid vaccine is currently available. In the present study we developed a bivalent vaccine against Salmonella Typhi and Paratyphi A using a bacterial ghost platform. Bacterial ghost cells (BGs) are bacteria-derived cell membranes without cytoplasmic contents that retain their cellular morphology, including all cell surface features. Furthermore, BGs have inherent adjuvant properties that promote an enhanced humoral and cellular immune reaction to the target antigen. Sodium hydroxide was used to prepare ghost cells of Salmonella Typhi and Paratyphi A. The bacterial ghost cells were characterised using electron microscopy. Then BALB/c mice were immunized three times (0th, 14th and 28th day) with the bivalent typhoidal bacterial ghost cells. Haematological study of adult mice throughout immunization period reflected that the immunogen was safe to administer and does not affect the animals' health. After complete immunization, we found significant serum antibody titter against whole cell lysate, outer membrane protein and lipopolysaccharide of both bacteria, and cell-mediated immunity was observed in an ex-vivo experiment. CD4+, CD8a+ and CD19+ splenic cell populations were increased in immunized animals. Bivalent Typhoidal ghost cell immunized mice showed better survival, less bacterial colonization in systemic organs, and less inflammation and/or destruction of tissue in histopathological analysis than non-immunized control mice.Serum antibodies of immunized animals can significantly inhibit bacterial motility and mucin penetration ability with better killing properties against Salmonella Typhi and Paratyphi A. Furthermore, significant passive protection was observed through the adoptive transfer of serum antibody and lymphocytes of immunized animals to naïve animals after bacterial infection. In summary, Bivalent Typhoidal Bacterial Ghost cells (BTBGs) enhances immunogenic properties and serves as a safe and effective prevention strategy against Salmonella Typhi and Paratyphi A.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18-24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation. METHODS: Indigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders. RESULTS: 11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87-1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16-1.35) and specified (HR 0.89; 95% CI: 0.49-1.62) from unspecified causes (HR 1.13; 95% CI: 0.86-1.49). During the baseline period before PPV23 vaccination (12-18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30-2.28). CONCLUSION: In this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18-30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.

BACKGROUND: Streptococcus pneumoniae (Spn) is a common respiratory pathogen and the main cause of bacterial pneumonia, meningitis, and bacteremia, acute otitis media. Imported 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in China and introduced in Shanghai in 2017. We aim to describe PCV13 vaccination trends and pneumonia incidence of children under 5 from 2017 to 2020, then estimate the effectiveness of PCV13 against community-acquired pneumonia (CAP) in children under 5 in Shanghai, China. METHODS: By calculating propensity scores with logistic regression, a comparison group was formed by frequency matching one unvaccinated child to one vaccinated child. For matching, we used the nearest-neighbor matching algorithm and exact matching, and then created distinct matched analysis sets for two cohorts. A Kaplan-Meier analysis was conducted to measure the cumulative incidence of all-cause pneumonia in both groups and used the log-rank test to assess the differences between the two cumulative incidence curves. Cox proportional hazards regression was used to compare the adjusted hazard ratios (HR) of differences in all-cause pneumonia between the two groups. RESULTS: Children received three or more doses PCV13 accounted for 85.7% of all vaccinated children. The incidence of pneumonia in Shanghai's Songjiang district decreased rapidly from 2017, when PCV13 vaccination presented an overall increasing trend. The estimated vaccine effectiveness against visits for all-cause pneumonia was 19% (95% CI: 3 to 32) after the first dose in children vaccinated with at least one dose of PCV13. The protective effectiveness of PCV13 was found to be higher for hospitalized pneumonia (30%, 95% CI: 5% to 49%) than for outpatient pneumonia (19%, 95% CI: 4% to 32%). CONCLUSIONS: PCV13 vaccination among children aged 0-5 years substantially reduced the incidence of all-cause pneumonia. Direct immunization of children under 5 years is an effective strategy to combat outpatient pneumonia, and hospitalized pneumonia.

BACKGROUND: Although the effectiveness of coronavirus disease 2019 (COVID-19) vaccines is a crucial public health concern, evidence from Western Pacific countries is limited, including Japan. This study aimed to estimate the COVID-19 vaccines effectiveness (VE) against infection during the Delta variant predominance (July-September 2021) in Japan. METHODS: We performed a test-negative study using COVID-19 test data of ≥20-year-old residents in four municipalities who were tested in medical institutions between July 1 and September 30, 2021. We extracted COVID-19 test data from healthcare claims data, and the vaccination status at the testing date was ascertained using the Vaccination Record System data. Confirmed positive cases were identified using data from the national system for COVID-19, Health Center Real-time Information-sharing System on COVID-19. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. VE was calculated as (1 - odds ratio) × 100%. RESULTS: This study included 530 positive and 15,650 negative results. Adjusted manufacturer-unspecified VE was 4.1% (95% confidence interval [CI], -36.5-32.6) at 0-13 days after the first dose, 45.2% (95% CI, 13.4-65.3) at ≥14 days after the first dose, 85.2% (95% CI, 69.9-92.7) at 0-13 days after the second dose, and 79.6% (95% CI, 72.6-84.8) at ≥14 days after the second dose. In addition, the VE after the second dose was highest at 14-34 days after the dose (VE, 89.1%; 95% CI, 80.5-93.9). CONCLUSIONS: High real-world effectiveness of COVID-19 vaccines, especially two doses, against infection during the Delta variant predominance in Japan was confirmed.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare disorder described after vaccination with adenoviral vector-based COVID-19 vaccines. Co-occurring thrombosis with thrombocytopenia reported after vaccination can be a proxy for identification of TTS. METHODS: Descriptive database review of all cases of co-occurring (within 42 days) thrombosis with thrombocytopenia in participants in Ad26.COV2.S clinical trials or recipients of Ad26.COV2.S in real-world clinical practice. Cases were retrieved from Janssens' clinical trial and Global Medical Safety databases. RESULTS: There were 34 cases of co-occurring thrombosis with thrombocytopenia in Ad26.COV2.S recipients (46 per 100,000 person-years) and 15 after placebo (75 per 100,000 person-years) in clinical trials. Among Ad26.COV2.S recipients, mean age at the time of the event was 63 years (range 25-85), 82 % were male, mean time-to-onset 112 days (range 8-339) post-last Ad26.COV2.S dose, 26 events occurred post-dose-1, and 7 within a 28-day risk window post-vaccination. Diagnostic certainty was evaluated using Brighton Collaboration, US Centers for Disease Control and Prevention, and European Medicines Agency Pharmacovigilance Risk Assessment Committee case definitions. One case met the highest level of diagnostic certainty for all 3 definitions. There were 355 spontaneous reports of co-occurring thrombosis with thrombocytopenia in the Global Medical Safety database, 47 % males, 85 % within 28-days after vaccination. Twenty-seven cases met the highest level of diagnostic certainty for all definitions, 21 female, 19 with cerebral venous sinus thrombosis, age-range 18-68 years. Time-to-onset was 7-14 days post-vaccination in 20 cases. There were 8 fatalities. CONCLUSION: TTS induced by Ad26.COV2.S is very rare. Most co-occurring thrombosis with thrombocytopenia does not constitute TTS.

BACKGROUND: Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. METHODS: Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19-associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. RESULTS: We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. CONCLUSIONS: During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19-associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.

INTRODUCTION: Vaccines, especially live attenuated vaccines, in children with JIA pose a great challenge due to both potential lower immunogenicity and safety as a result of immunosuppressive treatment. For many years, in the Netherlands, JIA patients receive a measles-mumps-rubella (MMR) booster vaccine at the age of nine years as part of the national immunization program. OBJECTIVES: To study long-term humoral immunoprotection in a large cohort of JIA patients who received the MMR booster vaccine while being treated with immunomodulatory therapies at the Wilhelmina Children's Hospital in Utrecht, the Netherlands. METHODS: MMR-specific IgG antibody concentrations in stored serum samples of vaccinated JIA patients were determined with chemiluminescent microparticle immunoassays (CMIA). Samples were analyzed five years after MMR booster vaccination and at last available follow-up visit using both crude and adjusted analyses. Additional clinical data were collected from electronic medical records. RESULTS: In total, 236 samples from 182 patients were analyzed, including 67 samples that were available five years post-vaccination, and an additional 169 samples available from last visits with a median duration after vaccination of 6.9 years (IQR: 2.8-8.8). Twenty-eight patients were using biologic disease-modifying antirheumatic drugs (bDMARDS) of whom 96% anti-TNF agents and 4% tocilizumab. Percentages of protective antibody levels against measles after five years were significantly lower for patients who used bDMARD therapy at vaccination compared to patients who did not: 60% versus 86% (P = 0.03). For mumps (80% versus 94%) and rubella (60% versus 83%) this difference did not reach statistical significance (P = 0.11 and P = 0.07, respectively). Antibody levels post-vaccination decreased over time, albeit not significantly different between bDMARD users and non-bDMARD users. CONCLUSION: The MMR booster vaccine demonstrated long-term immunogenicity in the majority of children with JIA from a large cohort, although lower percentages of protective measles antibody levels were observed in bDMARD users. Hence, it might be indicated to measure antibody levels at least five years after MMR booster vaccination in the latter group and advice an extra booster accordingly.

The viral safety of biological products is ensured by tests throughout the production chain, and, for certain products, by steps in the manufacturing process enabling the elimination or inactivation of viruses. Current testing programs include sample inoculation in animals and embryonic eggs. Following the 3Rs principles of replacement, reduction, and refinement of animal-use methods, such techniques are intended to be replaced not only for ethical reasons but also because of their inherent technical limitations, their long turnaround times, and their limits in virus detection. Therefore, we have compared the limit and range of sensitivity of in vivo tests used for viral testing of cells with a transcriptomic assay based on Next Generation Sequencing (NGS). Cell cultures were infected with a panel of nine (9) viruses, among them only five (5) were detected, with variable sensitivity, by in vivo tests. The transcriptomic assay was able to detect one (1) infected cell among 103 to 107 non-infected cells for all viruses assessed, including those not detected by the conventional in vivo tests. Here we show that NGS extends the breath of detection of viral contaminants compared to traditional testing. Collectively, these results support the replacement of the conventional in vivo tests by an NGS-based transcriptomic assay for virus safety testing of cell substrates.

BACKGROUND: Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). METHODS: Infants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). RESULTS: S. pneumoniae was isolated from 883/1063 NPS collected at 1-23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6-97.6%) of PCV10 recipients and 88.6% (95%CI 80.1-94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2-29.5) than PCV13 recipients (9.3%, 95%CI 4.1-17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19-2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%). CONCLUSION: Even after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes. The study is registered with ClinicalTrials.gov (CTN NCT01619462).

BACKGROUND: Evidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant. METHODS: This prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19. RESULTS: A total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %-64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60-139 days). Effectiveness waned from 77.7 % at 7-29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days. CONCLUSION: In a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307).

OBJECTIVE: To assess the timeliness and risk factors for the delay in the uptake of the hepatitis B birth dose among Indian children aged 0-59 months. Information regarding whether the children received the birth dose and the time of receiving it was recorded based on the vaccination card available at the time of the National Family Health Survey (NFHS). METHODS: Using data from the fourth and fifth round of India's National Family Health Survey (NFHS), the percentage of uptake and timely receipt of the hepatitis B birth dose were obtained by background characteristics and at the sub-national level (state). Multinomial logistic regression analysis was used to examine the risk factors. This study further performed a negative binomial regression estimation to predict the probability of receiving the birth dose at each day within a multivariable framework. RESULTS: It was found that approximately 34 % of the children who received the birth dose and the timing of receiving the birth dose was made available through the vaccination card were administered the dose within 24-hours during 2015-16. However, the percentage increased to 51.91 % during 2019-21. During 2019-21, Ladakh had the highest proportion (85.03 %) of children receiving the dose within 24-hours, followed by Jammu & Kashmir with 78 %, and Arunachal Pradesh with 68 %. Mother's education, economic status of the child's family and region (children belong from) were found to be significant predictors in delay of receiving the birth dose within 24 hours. CONCLUSION: Results indicated a need for targeted interventions to improve the coverage and timeliness in the uptake of this critical vaccine dose in the country. These interventions could include strategies such as strengthening the healthcare system, improving awareness among parents and healthcare providers, addressing logistical challenges in vaccine delivery, and promoting community engagement and education on importance of timely vaccination.

BACKGROUND: The effect of the timing of additional doses and the long-term persistence of lyophilized inactivated tissue culture hepatitis A (HA) vaccine (Aimmugen®) on antibodies is unknown. METHODS: A single-center, cross-sectional, observational study was conducted in collaboration with the Japan Air Self-Defense Force, whose personnel were immunized with Aimmugen® when deployed to endemic areas. Patients who consented to this study after a medical examination with blood sampling between June 2022 and February 2023 were included; HA-IgG level in the residual serum was measured using the chemiluminescent immunoassay method. The exact vaccination history was investigated based on immunization records maintained by the Ministry of Defense, and a questionnaire was used to collect confounding factors. RESULTS: Of the 181 participants observed, 49 were in the unvaccinated group, and 132 were in the vaccinated group. Out of the vaccinated group, 6.8 % received either one or two doses, 40.9 % received three doses, and 52.3 % received more than four doses. IgG antibody titers (S/CO value) in each group (0, 1 or 2, 3, and over 4) increased in a frequency-dependent manner, with those vaccinated over four times showing significantly higher IgG antibody titers than all other groups (0.19 ± 0.10 vs 3.66 ± 3.00 vs 7.63 ± 3.57 vs 10.57 ± 1.86, respectively). When the number of months elapsed from the last vaccination to the date of blood collection in each group was plotted against IgG antibody titer, the slope of the regression line flattened out from a decreasing trend in the order 1 or 2, 3, over 4. CONCLUSIONS: Three doses of Aimmugen® are efficacious, but four or more doses induce more robust and sustained antibody production. Additionally, four or more doses may be effective when there is a need to ensure long-term immunity or risk of prolonged exposure.

Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we report a recombinant bivalent COVID-19 vaccine containing the RBD proteins of the prototype strain and beta variant. Immunization studies in mice demonstrated that this bivalent vaccine had far greater immunogenicity than the ZF2001, a marketed monovalent recombinant protein COVID-19 vaccine, and exhibited good immunization effects against the original COVID-19 strain and various variants. Rhesus macaque challenge experiments showed that this bivalent vaccine drastically decreased the lung viral load and reduced lung lesions in SARS-CoV-2 (the causative virus of COVID-19)-infected rhesus macaques. In summary, this bivalent vaccine showed immunogenicity and protective efficacy that was far superior to the monovalent recombinant protein vaccine against the prototype strain and provided an important basis for developing broad-spectrum COVID-19 vaccines.

AIM: This paper investigates the prevalence and determinants of three main states of people's willingness to be vaccinated (WTBV) against COVID-19 - willing, unwilling and hesitant - and the occurrence and predictors of shifts between these states over time. Understanding the dynamics of vaccine intentions is crucial for developing targeted campaigns to increase uptake and emergency response preparedness. STUDY DESIGN: A panel survey consisting of 9 quarterly waves of data collected between April 2020 and January 2022. Baseline data included 24 952 adults from Germany, UK, Denmark, the Netherlands, France, Portugal, and Italy recruited from online panels to construct census-matched nationally representative samples. METHODS AND MEASURES: Self-reported COVID-19 vaccine intention was the main outcome. Multinomial logit random effects models were used to analyze the relationships of interest. All results reported as relative risk ratios (RRR). RESULTS: Hesitancy to get vaccinated was the most unstable vaccine intention, with on average 42% of ever hesitant respondents remaining in this state through future waves, followed by the 'unwilling' (53%) and 'willing (82%). Following COVID-19 news, trust in information from the government, GPs and the WHO, risk preferences, risk perceptions, and confidence in vaccines (or lack thereof) predicted vaccination intention reversals. Risk preferences acted both as an impediment and as a facilitator for the vaccine uptake depending on the initial vaccine intention. CONCLUSIONS AND RELEVANCE: This study revealed the dynamic nature of COVID-19 vaccine intentions and its predictors in 7 European countries. The findings provide insights to policymakers for designing more effective communication strategies, particularly targeted at hesitant and unwilling to vaccinate population groups, to increase vaccine uptake for future public health emergencies.

BACKGROUND: In November 2019, the US Advisory Committee on Immunization Practices recommended shared clinical decision-making (SCDM) for use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent elderly adults. The impact of SCDM on PCV13 use in this population, immunocompromised persons, and vulnerable subgroups has not been well documented. METHODS: Using Medicare Research Identifiable Files (01/2018 - 09/2020), monthly uptake of pneumococcal vaccine (PCV13, 23-valent pneumococcal polysaccharide vaccine [PPSV23]) was identified among fee-for-service beneficiaries aged ≥ 65 years with Part B coverage and no evidence of prior PCV13. Uptake was stratified by vaccine, risk profile, and demographics. RESULTS: Among the > 12 M beneficiaries included each month, PCV13 uptake declined from > 70% of pneumococcal vaccinations before SCDM to < 60% after SCDM (02/2020). Reductions in PCV13 uptake were consistent across vulnerable subgroups as well as immunocompromised persons. CONCLUSIONS: PCV13 use decreased among immunocompetent and immunocompromised persons alike, despite continued routine PCV13 recommendation for the latter group.

BACKGROUND: Seasonal influenza vaccines (SIVs) can protect against influenza and substantially reduce the risk of influenza-related hospitalizations and fatalities in children. This study aimed to assess parental attitudes towards SIVs in the Eastern Mediterranean region (EMR). METHODS: Through an anonymous online survey conducted in 19 countries in the EMR, parents or caregivers over 18 years who had at least one child above 6 months filled out the Parent Attitudes about Childhood Vaccines questionnaire. As data had two levels; country and individual factors, we utilized multilevel binary logistic regression models. RESULTS: In total, 6992 respondents filled out the questionnaire. Of them, 47.4 % were residents of middle-income countries, 72.4 % of the mothers were between 26 and 45 years old, 56.5 % had at least a university degree, and approximately 51.6 % were unemployed. Nearly 50.8 % of the respondents were hesitant to vaccinate their children against seasonal influenza. Parental attitudes towards seasonal influenza vaccination differed significantly between countries, p < 0.001. The main predictors of parental seasonal influenza vaccine hesitancy (VH) were parents vaccination (odds ratio (OR) = 0.42, 95 % CI = 0.32-0.55, p < 0.001)), the mother's education if mother educated vs. who did not receive any education (OR ranged from 0.48 to 0.64, p < 0.05), living in low-income countries (OR = 0.52, 95 % CI = 0.35-0.77, p < 0.01), mountain residence (0.69, 95 % CI = 0.49-0.99, p < 0.05), health workers as a source of information (OR = 0.70, 95 % CI = 0.58-0.85, p < 0.001), children vaccination against COVID-19 (OR = 0.52, 95 % CI = 0.41-0.65, p < 0.001), not receiving routine vaccinations (OR = 1.93, 95 % CI = 1.09-3.44, p = 0.025), and if parents respondents could not remember whether their child had suffered from seasonal influenza in the previous year (OR = 1.57, 95 % CI = 1.33-1.84, p < 0.001). CONCLUSION: A high seasonal influenza VH rate was found in the EMR. Health authorities should implement different interventions targeting the identified modifiable risk factor to increase vaccine uptake among children, especially those at risk of complication from seasonal influenza infection.

BACKGROUND: Hospital settings represent an opportunity to offer and/or promote childhood vaccination. The purpose of the systematic review was to assess the effectiveness of different hospital-based strategies for improving childhood vaccination coverage. METHODS: A systematic search of multiple bibliographic databases, thesis databases, and relevant websites was conducted to identify peer-reviewed articles published up to September 20, 2021. Articles were included if they evaluated the impact of a hospital (inpatient or emergency department)-based intervention on childhood vaccination coverage, were published in English or French, and were conducted in high-income countries. High quality studies were included in a narrative synthesis. RESULTS: We included 25 high quality studies out of 7,845 unique citations. Studies focused on routine, outbreak, and influenza vaccines, and interventions included opportunistic vaccination (i.e. vaccination during hospital visit) (n = 7), patient education (n = 2), community connection (n = 2), patient reminders (n = 2), and opportunistic vaccination combined with patient education and/or reminders (n = 12). Opportunistic vaccination interventions were generally successful at improving vaccine coverage, though results ranged from no impact to vaccinating 71 % of eligible children with routine vaccines and 9-61 % of eligible children with influenza vaccines. Interventions that aimed to increase vaccination after hospital discharge (community connection, patient education, reminders) were less successful. CONCLUSIONS: Some interventions that provide vaccination to children accessing hospitals improved vaccine coverage; however, the baseline coverage level of the population, as well as implementation strategies used impact success. There is limited evidence that interventions promoting vaccination after hospital discharge are more successful if they are tailored to the individual.

BACKGROUND: Traditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code "tree" and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance. RESULTS: Analysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1-3, p = 0.0001-0.0007), influenza (Days 35-56, p = 0.0001), cough (Days 44-55, p = 0.0002), and COVID-19 (Days 52-56, p = 0.0004). CONCLUSIONS: For Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the "tree."

PURPOSE: This systematic review presents cost-effectiveness studies of rotavirus vaccination in high-income settings based on dynamic transmission modelling to inform policy decisions about implementing rotavirus vaccination programmes. METHODS: We searched CEA Registry, MEDLINE, Embase, Health Technology Assessment Database, Scopus, and the National Health Service Economic Evaluation Database for studies published since 2002. Full economic evaluation studies based on dynamic transmission models, focusing on high-income countries, live oral rotavirus vaccine and children ≤ 5 years of age were eligible for inclusion. Included studies were appraised for quality and risk of bias using the Consensus on Health Economic Criteria (CHEC) list and the Philips checklist. The review protocol was prospectively registered with PROSPERO (CRD42020208406). RESULTS: A total of four economic evaluations were identified. Study settings included England and Wales, France, Norway, and the United States. All studies compared either pentavalent or monovalent rotavirus vaccines to no intervention. All studies were cost-utility analyses that reported incremental cost per quality-adjusted life year (QALY) gained. Included studies consistently concluded that rotavirus vaccination is cost-effective compared with no vaccination relative to the respective country's willingness to pay threshold when herd protection benefits are incorporated in the modelling framework. CONCLUSIONS: Rotavirus vaccination was found to be cost-effective in all identified studies that used dynamic transmission models in high-income settings where child mortality rates due to rotavirus gastroenteritis are close to zero. Previous systematic reviews of economic evaluations considered mostly static models and had less conclusive findings than the current study. This review suggests that modelling choices influence cost-effectiveness results for rotavirus vaccination. Specifically, the review suggests that dynamic transmission models are more likely to account for the full impact of rotavirus vaccination than static models in cost-effectiveness analyses.

BACKGROUND AND OBJECTIVES: A cost-utility analysis was conducted to assess the efficiency of implementing a PCV20 vaccination strategy in the Spanish adult population older than 60 years, for the prevention of non-bacteremic pneumococcalpneumonia (NBP) and invasive pneumococcal disease (IPD). METHODS: A Markov model, with annual cycles and a time horizon of 10 years was used. The analysis population was stratified by age and risk groups. The comparator was the sequential vaccination with the 15-valent pneumococcal conjugate vaccine (PCV15) followed by one dose of the pneumococcal polysaccharide vaccine (PPV23). The base case analysis was performed from the National Healthcare System (NHS) perspective including direct costs (€2018) and applying a discount of 3% to future costs and outcomes. Alternative scenarios explored a shorter time horizon (5 years), the societal perspective and other available vaccination strategies. All the parameters and assumptions were validated by a panel of experts. To evaluate the robustness of the model, deterministic and probabilistic sensitivity analyses (PSA) were carried out. RESULTS: The results of the study showed that the vaccination strategy with PCV20 is a dominant option compared to the sequential regimen (PCV15 + PPSV23), resulting in direct cost savings of €85.7 M over 10 years, with a small increase in quality-adjusted life years (QALYs). PCV20 vaccination avoided 2,161 cases of IPD, 19,470 of NBP and 3,396 deaths and according to the PSA, the probability of PCV20 being cost-effective compared to a sequential regimen (PCV15 + PPSV23) was 100%. CONCLUSIONS/RECOMMENDATIONS: In the Spanish adult population older than 60 years, the vaccination strategy with one dose of PCV20 is more effective and less expensive (dominant) than vaccination with a sequential schedule with PCV15 and PPSV23.

BACKGROUND: Many signals of menstrual disturbances as possible side effects of vaccination against COVID-19 have been reported. Our objective was to compare the risk of menstrual disturbances before and after vaccination among women aged 18-30 years in Oslo, Norway. METHODS: We used electronic questionnaires to collect reports of menstrual disturbances from 3972 women aged 18-30 years, participating in the population-based Norwegian Young Adult Cohort. We examined the occurrence of menstrual disturbances (heavier bleeding than usual, prolonged bleeding, shorter interval between menstruations, longer interval between menstruations, spot bleedings, stronger pain during menstruation, period pain without bleeding) before and after the first and second dose of COVID-19 vaccine. Relative risks (RR) according to vaccination were estimated using a self-controlled case-series design. We performed additional analyses stratified by vaccine brand, contraception/hormone use, and presence of gynecological condition(s). RESULTS: The prevalence of any menstrual disturbance was 36.7 % in the last menstrual cycle prior the first vaccine dose. The RR for heavier bleeding than usual was 1.90 (95 % CI: 1.69-2.13) after the first vaccine dose and 1.84 (95 % CI 1.66-2.03) after the second dose. Increased risks of prolonged bleeding, shorter interval between menstruations, and stronger pain during menstruation were also observed after both doses. The RRs did not differ with vaccine brand, contraception/hormone use, or presence of gynecological condition(s) for any of the menstrual disturbances. CONCLUSION: Menstrual disturbances were common regardless of vaccination. We found increased risk of menstrual disturbances after vaccination, particularly for heavier bleeding than usual, prolonged bleeding, shorter interval between menstruations, and stronger period pain. In the future, menstrual characteristics should be included in vaccine trials.

BACKGROUND: Prevention of infectious diseases among children is crucial to improve child health and survival. However, many countries in Sub-Saharan Africa struggle to achieve vaccination targets due to supply chain challenges, which lead to vaccine shortages, stockouts, and increased costs. We evaluated the effects of aerial logistics (centralized storage and delivery by drones) on vaccine stock, stockouts, vaccination coverage and vaccine preventable outcomes in the Western North Region of Ghana. METHODS: The study combined retrospective quasi-experimental and cross-sectional designs to evaluate supply chain, programmatic, and clinical outcomes. Surveys to health providers were used to collect information from a random sample of 156 facilities, and secondary data on vaccination coverage and clinical outcomes was analyzed at the district level for the years 2017-2021. RESULTS: Facilities served by aerial logistics reported significant reductions in the duration of vaccine stockouts (30 %, p-value < 0.05), as well as in the frequency of missed opportunities for vaccination (44 %, p-value < 0.05). Being served by aerial logistics was associated with increased satisfaction with access to vaccines. Significant differences in vaccination coverage were found for most vaccines, in a range between 13.1 and 37.5 percentage points in vaccination coverage for served districts. Infectious diarrhea cases in children between 5 and 9 years old were reduced by 41.6 % (p-value < 0.05). CONCLUSION: End-to-end aerial logistics appears as an effective tool to improve the performance of the supply chain for vaccines. The strategy potentially increases the resilience of the health system and contributes to increased vaccination coverage and higher levels of satisfaction among providers in the Western North Region of Ghana.

An elevated risk of venous thromboembolism (VTE) following a first dose of the ChAdOx1 adenovirus-vectored vaccine was found in a national epidemiological study in England using routine discharge diagnosis codes. Separately, the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) was identified using haematological criteria based on presence of thrombocytopenia, significantly elevated D-dimers and development of anti-PF4 antibodies. To re-evaluate risk estimates using haematological criteria, we obtained the haematology results for hospital admitted patients aged 18-64 years in 43 National Health Service trusts in England who were included in the national epidemiological study. Diagnoses were confirmed and haematological parameters obtained from local records without knowledge of vaccination status. The haematological parameters in patients admitted for a confirmed VTE following ChAdOx1 or BNT162b2 mRNA vaccination were then compared with those in a randomly selected 40% sample of unvaccinated patients with VTE. Overall, 12 (14%) of the 84 vaccinated cases had a diagnosis compatible with VITT, 11 after a first dose of ChAdOx1 and one after a first dose of BNT162b2. Thrombocytopenia (platelet count <150 × 109/L) occurred in 17 vaccinated (20%) and 4 (4%) of 108 unvaccinated patients, with all 6 cases of severe thrombocytopenia (<50 × 109/L) occurring within 42 days of a first dose of ChAdOx1. The attributable risk estimates for a cerebral venous thrombosis (CVT) or other VTE with thrombocytopenia after a first dose of ChAdOx1 vaccine were 2.82 and 9.62 per million doses respectively. However, elevated risks were also found after a first dose of ChAdOx1 for VTE without thrombocytopenia with relative incidences for CVT and other VTE of 2.67 (1.77-3.77) and 1.93 (1.57-2.35) respectively. While we identified a distinct population with features of VITT within 42 days of receiving ChAdOx1 vaccination, confirming current diagnostic criteria, we also found evidence of an increased risk of a VTE without thrombocytopenia after ChAdOx1 vaccine.

Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29-32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.

BACKGROUND: COVID-19 vaccine hesitancy is known to be more pronounced among young people. However, there are a lack of studies examining determinants of COVID-19 vaccination intention in the general population in this young age-group in Switzerland, and in particular, studies investigating the influence of information sources and social networks on vaccination intention are missing. METHODS: The cross-sectional study "COVIDisc - Discussion with young people about the corona pandemic" provided the opportunity to investigate COVID-19 vaccination intention in 893 individuals aged 15-34 years from the cantons of Zurich, Thurgau, and Ticino in Switzerland. An online survey was administered between 10 November 2020 and 5 January 2021. Associations of public information sources and conversations about COVID-19 with COVID-19 vaccination intention were analyzed with multivariable logistic regression and mediation analysis using generalized structural equation modeling. RESULTS: 51.5% of the participants intended or probably intended to get vaccinated once the vaccine would be available. Using print or online news (AOR 1.50, 95% CI 1.09-2.07) as an information source and having conversations about the COVID-19 vaccine (AOR 2.09, 95% CI 1.52-2.87) increased participants' COVID-19 vaccination intention. The effects of female gender (b = -0.267, p = 0.039) and risk perception (b = 0.163, p = 0.028) were partially mediated by having conversations about the COVID-19 vaccine. The effects of age (b = -0.036, p = 0.016), secondary educational level (b = 0.541, p = 0.010) and tertiary educational level (b = 0.726, p = 0.006) were fully mediated via having conversations about the COVID-19 vaccine. CONCLUSIONS: Conversations and campaigns should start even before vaccines become available. Our data support interventions for young women and less educated people using social norms and supporting information seeking with news. Trust and risk perceptions are essential foundations for vaccine intentions.

INTRODUCTION: In the summer of 2022, a vaccination campaign for the prevention of poliomyelitis was launched and "The CDC recommend that all children be vaccinated against polio, or poliomyelitis". The scientific community is on the alert for new cases of polio, which is spreading. Although polio seemed to have been almost completely eradicated throughout the world, the disease has surprisingly reappeared in some Western countries. The risk of international spread of poliovirus remains a Public Health Emergency of International Concern (PHEIC). METHOD: The authors reviewed recent polio cases in some western countries which have caused significant public health concern and they underline the meaning and weight of this issue emphasizing the importance of vaccination. DISCUSSION: In June 2022, the British authorities announced that they had detected traces of a form of polio derived from a vaccine strain in the wastewater of some London boroughs. Although no cases of disease were identified, the British government immediately announced that it was proceeding to reinstate polio vaccination for all children. A few weeks later, on July 18, 2022, the New Jersey Department of Health notified the CDCP of the detection of type-2 poliovirus in an unvaccinated young man in the New York metropolitan area. This case immediately triggered an appeal from the CDCP to get vaccinated and, above all, to vaccinate children. Low vaccination coverage means that the population is constantly at risk of further cases of paralytic poliomyelitis. CONCLUSION: The appeal to vaccinate children against polio is crucial, as prevention through vaccination is the only defense against the disease. We think that an efficient vaccination campaign can positively influence the process of eliminating the virus. At the same time, however, it demonstrates that simply lowering one's guard can quickly lead to a resurgence of polio cases. Hence, until polio is eradicated, we can be sure that contagion by the wild virus and the risk of vaccine-derived poliovirus will remain possible.

BACKGROUND: In December 2020 the U.S. began a massive COVID-19 vaccination campaign, an action that researchers felt could catalyze inequalities in COVID-19 vaccination utilization. While vaccines have the potential to be accessible regardless of social status, the objective of this study was to examine how and when socioeconomic status (SES) and racial/ethnic inequalities would emerge in vaccination distribution. METHODS: Population vaccination rates reported at the county level by the Centers for Disease Control and Prevention across 46 states on 3/30/2021. Correlates included SES, the share of the population who were Black, Hispanic, Female, or aged ≥65 years, and urbanicity (thousands of residents per square mile). Multivariable-adjusted analyses relied on zero-inflated negative binomial regression to estimate the odds of providing any vaccine, and vaccination rate ratios (aVRR) comparing the distribution rate for vaccinations across the U.S. RESULTS: Across the U.S., 16.3 % of adults and 37.9 % of adults aged 65 and older were vaccinated in lower SES counties, while 20.45 % of all adults and 48.15 % of adults aged 65 and older were vaccinated in higher SES counties. Inequalities emerged after 41 days, when < 2 % of Americans were vaccinated. Multivariable-adjusted analyses revealed that higher SES was associated with improved vaccination distribution (aVRR = 1.127, [1.100-1.155], p < 1E-06), while increases in the percent reporting Black or Hispanic race/ethnicity was associated with lower vaccination distribution (aVRR = 0.998, [0.996-0.999], p = 1.03E-04). CONCLUSIONS: Social inequalities in COVID-19 vaccines reflect an inefficient and inequitable distribution of these technologies. Future efforts to improve health should recognize the central role of social factors in impacting vaccine delivery.

BACKGROUND: The Immunization Agenda 2030 (IA2030) Impact Goal 1.1. aims to reduce the number of future deaths averted through immunization in the next decade. To estimate the potential impact of the aspirational coverage targets for IA2030, we developed an analytical framework and estimated the number of deaths averted due to an ambitious vaccination coverage scenario from 2021 to 2030 in 194 countries. METHOD: A demographic model was used to determine annual age-specific mortality estimates associated with vaccine coverage rates. For ten pathogens (Hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, yellow fever), we derived single measures of country-, age-, and pathogen-specific relative risk of deaths conditional upon coverage rates, leveraging the data from 18 modeling groups as part of the Vaccine Impact Model Consortium (VIMC) for 110 countries. We used a logistic regression model to extrapolate the relative risk estimates to countries that were not modeled by VIMC. For four pathogens (diphtheria, tetanus, pertussis and tuberculosis), we used estimates from the Global Burden of Disease 2019 study and existing literature on vaccine efficacy. A future scenario defining years of vaccine introduction and scale-up needed to reach aspirational targets was developed as an input to estimate the long-term impact of vaccination taking place from 2021 to 2030. FINDINGS: Overall, an estimated 51.5 million (95 % CI: 44.0-63.2) deaths are expected to be averted due to vaccinations administered between the years 2021 and 2030. With immunization coverage projected to increase over 2021-2030 an average of 5.2 million per year (4.4-6.3) deaths will be averted annually, with 4.4 million (3.9-5.1) deaths be averted for the year 2021, gradually rising to 5.8 million (4.9-7.5) deaths averted in 2030. The largest proportion of deaths is attributed to Measles and Hepatitis B accounting for 18.8 million (17.8-20.0) and 14.0 million (11.5-16.9) of total deaths averted respectively. INTERPRETATION: The results from this global analysis demonstrate the substantial potential mortality reductions achievable if the IA2030 targets are met by 2030. Deaths caused by vaccine preventable diseases disproportionately affect LMICs in the African region.