BACKGROUND: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. METHODS: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). RESULTS: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

OBJECTIVES: Older adults face increased risks from infectious diseases which are often preventable with vaccines. The current study examines demographic variation in vaccine hesitancy among older adults in North Dakota. METHODS: A mailed survey assessing age, gender, years of education, self-rated health, rurality, and political leaning as well as vaccine attitudes and vaccine acceptance was conducted with 739 older adults (65+), oversampled from rural counties. RESULTS: Vaccine hesitant attitudes were significantly higher among rural and politically-conservative older adults; whereas, vaccine acceptance was significantly higher among older, healthier, and politically-liberal older adults. Vaccine attitudes were significantly associated with vaccine acceptance and mediated the association between political leaning and vaccine acceptance. DISCUSSION: These findings highlight the demographic characteristics predictive of older adults' vaccine attitudes and acceptance. By better understanding the nuanced factors leading to hesitation to be vaccinated, practitioners can develop strategies to increase vaccination rates among this at-risk population.

BACKGROUND: New prevention strategies for respiratory syncytial virus (RSV) are emerging, but it is unclear if they will be cost-effective in low- and middle-income countries. We evaluated the potential impact and cost-effectiveness of two strategies to prevent RSV disease in young children in Vietnam. METHODS: We used a static cohort model with a finely disaggregated age structure (weeks of age <5 years) to calculate the RSV disease burden in Vietnam, with and without a single dose of maternal vaccine (RSVpreF, Pfizer) or of monoclonal antibody (Nirsevimab, Sanofi, Astra Zeneca). Each strategy was compared to no pharmaceutical intervention, and to each other. We assumed both strategies would be administered year round over a ten-year period. The primary outcome measure was the cost per disability-adjusted life year (DALY) averted, from a societal perspective. We ran probabilistic and deterministic uncertainty analyses. RESULTS: With central input assumptions for RSVpreF vaccine ($25/dose, 69 % efficacy, 6 months protection) and Nirsevimab ($25/dose, 77 % efficacy, 5 months protection), both options had similar cost-effectiveness ($3442 versus $3367 per DALY averted) when compared separately to no pharmaceutical intervention. RSVpreF vaccine had a lower net cost than Nirsevimab (net discounted cost of $213 m versus $264 m) but prevented fewer RSV deaths (24 % versus 31 %). Our results were very sensitive to assumptions about the dose price, efficacy, and duration of protection. At $5/dose and a willingness-to-pay threshold of 0.5 times the national GDP per capita, both prevention strategies are cost-effective. CONCLUSIONS: RSVpreF vaccine and Nirsevimab may be cost-effective in Vietnam if appropriately priced.

In a phase 2 safety and immunogenicity study of a chikungunya virus virus-like particle (CHIKV VLP) vaccine in an endemic region, of 400 total participants, 78 were found to be focus reduction neutralizing antibody seropositive at vaccination despite being ELISA seronegative at screening, of which 39 received vaccine. This post hoc analysis compared safety and immunogenicity of CHIKV VLP vaccine in seropositive (n = 39) versus seronegative (n = 155) vaccine recipients for 72 weeks post-vaccination. There were no differences in solicited adverse events, except injection site swelling in 10.3% of seropositive versus 0.6% of seronegative recipients (p = 0.006). Baseline seropositive vaccine recipients had stronger post-vaccination luciferase neutralizing antibody responses versus seronegative recipients (peak geometric mean titer of 3594 and 1728, respectively) persisting for 72 weeks, with geometric mean fold increases of 3.1 and 13.2, respectively. In this small study, CHIKV VLP vaccine was well-tolerated and immunogenic in individuals with pre-existing immunity. ClinicalTrials.gov Identifier: NCT02562482.

Mpox has affected many communities in the United States (U.S.), including people experiencing homelessness (PEH). Mpox vaccination has been an important tool to disrupt transmission and protect communities at risk of infection. To better understand mpox vaccine knowledge and attitudes, we surveyed 273 PEH and people accessing homeless service sites in San Francisco. Among 64 participants previously offered mpox vaccination, 38 (59 %) had received the vaccine. Among 209 participants not previously offered mpox vaccination, 108 (52 %) reported they would receive the vaccine. Vaccine acceptance was higher among transgender female participants and among male participants who reported male sex partner preference (MSM). Half of participants who declined vaccination identified that perception of personal risk and vaccine education may increase their likelihood of receiving an mpox vaccine. Leveraging trusted information sources to provide risk communication and vaccine education may increase vaccine uptake among PEH.

After the temporary end of COVID-19 in China in February 2023, the influenza epidemic peaked in March across many Chinese places. We recruited a total of 258 all-age subjects presenting influenza-like illness (ILI) in Shihezi city, China from January 1 to March 16, 2023, and tested for influenza virus infection. Using a test-negative design, we assessed influenza vaccine effectiveness (VE) of 56.3% (95% CrI: 13.6, 73.6) against medically attended, influenza illness during the delayed 2022/23 influenza epidemic. The findings contributed to the continuous monitoring of the influenza vaccine performance across the world, especially in the "post-COVID" pandemic era.

Some vaccines have a small risk of Guillain-Barré Syndrome (GBS), a rare autoimmune disorder characterized by paralysis if untreated. The CDC's Advisory Committee on Immunization Practices (ACIP) guidelines do not consider GBS a precaution for future vaccines unless GBS developed within six weeks after a tetanus-toxoid-containing vaccine or influenza vaccine. Our goal was to describe vaccine patterns before and after GBS diagnosis. We matched each of 709 patients diagnosed with GBS from 2002 to 2020 with Medicare supplemental insurance to 10 counterparts without GBS (1:10) on age and sex. Propensity score-based weighting balanced covariates between groups, and we estimated weighted mean cumulative counts (wMCC) of vaccines/person before and after GBS diagnosis. Among patients with GBS, 7% were diagnosed within 42 days after a vaccine. Prior to GBS diagnosis, the wMCC of vaccines per person was similar between GBS cases and matched counterparts, but after two years of follow-up, GBS patients received 21 fewer vaccines/100 people than counterparts (wMCC difference -0.21 vaccines/person, 95% CI -0.24 to -0.18); GBS patients received 16 vaccines/100 people while matched counterparts received 36/100. Vaccine use was reduced following GBS diagnosis despite no ACIP precaution for most (93%) patients in this study. The observed drop in vaccines after GBS diagnosis indicates a disconnect between clinical practice and current recommendations.

BACKGROUND: From 2008 to 2019, France has experienced a resurgence of measles epidemics. Surveillance data have shown that the proportion of cases vaccinated with two doses of measles-containing vaccine (MCV) increased with age, raising concerns about the duration of vaccine protection. Our objectives were to investigate age-stratified vaccine effectiveness (VE) for the second dose of MCV (MCV2) and to quantify protection levels over time. METHODS: We analyzed data on measles cases aged 2-31 years, reported via mandatory notification to the French measles surveillance system from October 2017 to September 2019. We estimated an age-stratified VE for MCV2 using the screening method, which compares the vaccination status of cases with that of the general population. We improved this method by accounting for natural immunity, exploring four scenarios with four possible levels of natural immunity in the population. In addition, we quantified the decay rate of protection over time, by fitting an exponential decay model among individuals vaccinated in early life. RESULTS: In the baseline analysis (absence of natural immunity), VE estimates were high in all age groups and decreased with age, from 99.6 % (95 % confidence interval: 99.3-99.8) in 2-5 years old to 91.4 % (85.1-95.0) in 26-31 years old. Accounting for natural immunity increased VE in the older age group to 93.2-99.2 % depending on the scenario. We estimated that VE was slowly decreasing over time, with an exponential decay rate of 0.0022/year (0.0017-0.0028), leading to VE of 96.7 % (96.0-97.4) 16 years after MCV2 vaccination. This decline was most compatible with scenario 2, a scenario of 4.4 % naturally immunized, non-vaccinated individuals in the 26-31 years old. CONCLUSION: Our study confirms the continued high effectiveness of two doses of MCV with only slight degradation, decades after immunization. These findings support the importance of achieving a very high vaccination coverage with 2 doses of MCV.

Socially and medically vulnerable groups (e.g., people 65 years or older, minoritized racial groups, non-telework essential workers, and people with comorbid conditions) experience barriers to COVID-19 prevention and treatment, increased burden of disease, and increased risk of death from COVID-19. Researchers are paying increased attention to social determinants of health (SDH) in explaining inequities in COVID-19-related health outcomes and rates of vaccine uptake. The purpose of the present manuscript is to identify clinically significant predictors of COVID-19 vaccine uptake among people who were socially and medically vulnerable to SARs-CoV-2 infection. Analysis was informed by the SDH framework and included a sample of 641 baseline surveys from participants in a clinical trial designed to increase COVID-19 testing. All participants were at high risk of developing COVID-19-related complications or dying from COVID-19. Following community-based participatory research principles, a well-established community collaborative board conducted every aspect of the study. Multiple logistic regressions were conducted to examine the relationships between individual and structural factors and COVID-19 vaccine uptake. In the final time adjusted model, we found that vaccine uptake was only predicted by specific individual-level factors: being 65 years and older, living with HIV/AIDS, and having previously received a flu vaccine or a COVID-19 test. Those reporting to believe in COVID-19-conspiracy theories were less likely to get the COVID-19 vaccine. More research is needed to identify predictors of vaccine uptake among people with comorbidities that make them more vulnerable to COVID-19 complications or death.

The U.S. Food and Drug Administration authorized use of mRNA COVID-19 bivalent booster vaccines on August 31, 2022. Currently, CDC's clinical guidance states that COVID-19 and other vaccines may be administered simultaneously. At time of authorization and recommendations, limited data existed describing simultaneous administration of COVID-19 bivalent booster and other vaccines. We describe simultaneous influenza and mRNA COVID-19 bivalent booster vaccine administration between August 31-December 31, 2022, among persons aged ≥6 months in the Vaccine Safety Datalink (VSD) by COVID-19 bivalent booster vaccine type, influenza vaccine type, age group, sex, and race and ethnicity. Of 2,301,876 persons who received a COVID-19 bivalent booster vaccine, 737,992 (32.1%) received simultaneous influenza vaccine, majority were female (53.1%), aged ≥18 years (91.4%), and non-Hispanic White (55.7%). These findings can inform future VSD studies on simultaneous influenza and COVID-19 bivalent booster vaccine safety and coverage, which may have implications for immunization service delivery.

The global distribution and ongoing evolution of type A swine influenza virus (IAV-S) continue to pose significant challenges against developing broadly protective vaccines to control swine influenza. This study focuses on the hemagglutinin (HA) consensus-based approach towards developing a more broadly protective swine influenza vaccine against various H3 strains circulating in domestic pig populations. By computationally analyzing >1000 swine H3 full-length HA sequences, we generated a consensus H3 and expressed it in the context of influenza A WSN/33 reverse genetics system. The derived recombinant chimeric swine influenza virus with the consensus H3 was inactivated and further evaluated as a potential universal vaccine in pigs. The consensus H3 vaccine elicited broadly active hemagglutination inhibition (HI) antibodies against divergent swine H3N2 influenza viruses including human H3N2 variant of concern, and strains belong to genetic clusters IV, IV-A, IV-B, IV-C, IV-D and IV-F. Importantly, vaccinated pigs were completely protected against challenge with a clinical swine H3N2 isolate in that neither viral shedding nor replication in lungs of vaccinated pigs were observed. These findings warrant further study of the consensus H3 vaccine platform for broad protection against diverse swine influenza viruses.

There is a major unmet need for strategies to improve the immunogenicity of vaccines to protect against highly pathogenic avian influenza strains with pandemic potential. This study tested the ability of adjuvants based on delta inulin (Advax™) alone or combined with a TLR9 agonist (Advax-CpG™) to enhance the immunogenicity of recombinant H5 hemagglutinin antigen expressed in insect cells (rH5HA) to protect mice against lethal influenza infection. The Advax-adjuvanted rH5HA induced high serum hemagglutination inhibition activity, as well as Th1 and Th2 cytokine secreting CD4 and CD8 T cells. Immunization protected mice against a lethal heterosubtypic H5N1 virus challenge. Mice immunized with an Advax-adjuvanted rHA2 stem antigen prepared by enzymatic cleavage of rH5HA produced serum antibodies devoid of hemagglutination inhibition activity, but these anti-HA2 antibodies were nevertheless able to transfer protection against lethal H1N1 or H3N2 infections to naïve mice. We hypothesize that the enhanced protection afforded by Advax-adjuvanted rH5HA may be mediated by the combination of neutralizing antibodies directed at the HA head, anti-HA2 stem antibodies plus memory CD4 + and CD8 + T cells. This outcome supports further development of the Advax-adjuvanted rH5 pandemic influenza vaccine platform.

BACKGROUND: Active surveillance systems for monitoring vaccine safety among pregnant women address some of the limitations of a current passive surveillance approach utilized in low- and middle-income countries (LMIC). However, few active surveillance systems in LMIC exist. Our study assessed the feasibility of utilizing three existing data collection systems in Kenya for active surveillance of maternal immunization and to assess the applicability of Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions that were initially developed for clinical trials within these systems. METHODS: We assessed applicability of GAIA case definition for maternal Tetanus Toxoid exposure, stillbirth, low birth weight, small for gestational age, Neonatal Invasive Blood Stream Infection (NIBSI), prematurity and neonatal death in two routine web-based health information systems (Kenya EMR and DHIS-2), and a web-based population-based pregnancy research platform (ANCOV1) in Kenya. RESULTS: All three HIS were capable of reporting selected outcomes to varying degrees of GAIA certainty. The ANCOV platform was the most robust in collecting and collating clinical data for effective maternal pharmacovigilance. The utilization of facility- and district-aggregated data limits the usefulness of DHIS-2 in pharmacovigilance as currently operationalized. While the Kenya EMR contained individual level data and meets the key considerations for effective pharmacovigilance, it was used primarily for HIV care and treatment records in a small proportion of health facilities and would require additional resources to expand to all antenatal care facilities and to link maternal and infant records. DISCUSSION: Population-based research studies may offer a responsive short-term option for implementing maternal vaccine pharmacovigilance in LMICs. However, the foundation exists for long-term capacity building within the national health electronic data systems to provide this critical service as well as ensure participation of the country in international studies on maternal vaccine safety.

Despite Brazil's tradition of successful mass immunization programs, the country has been experiencing alarming declines in vaccination coverage, especially among children. That is aggravated by the growth of anti-vaccine movements and the spread of health misinformation in social media in the last decade, which have worsened during the COVID-19 outbreak. Several reports link populism and far-right politicians to anti-vaccination support worldwide, which was also the case in Brazil during president Jair Bolsonaro's administration. This project aimed to identify the circulating pro and anti-vaccine narratives in Portuguese on Twitter, during a crucial decision-making period regarding childhood vaccination in Brazil, from December 9, 2021, until February 9, 2022. From the over one million tweets and four million retweets collected, we identified two well-defined groups, one in favor and another against vaccination. Within the sample, we selected 1500 influencer tweets with the highest impact (>500 retweets) and conducted content analysis. Although the pro-vaccine influencers were more retweeted than anti-vaxxer ones, we observed that anti-vaccine movements were more succesful in framing discussions on Twitter. The subject of COVID-19 was the target of political polarization embedded in populist, anti-science and anti-traditional media discourses promoted by anti-vaxxers. As a counterpart, the pro-vaccine influencers reacted inarticulately, focusing on criticizing the anti-vaccination actors, attitudes, and policies instead of promoting vaccines. Based on reults, we claim that a well-coordinated network of health communicators from science centers and health institutions, in partnership with properly briefed social media influencers and fact-checking sources, would more efectively pre-tempt the public about vaccine misinformation.

INTRODUCTION: Vaccine surveillance for children in England focuses on coverage at ages 1, 2, and 5 years. Previous studies exploring vaccine timeliness have used different arbitrary categories to define whether vaccines were received 'late' or 'on time'. This paper aims to provide more detailed and holistic information on timing and patterns of vaccine uptake across the childhood immunisation schedule in England. METHODS: We included all children born in England between 2006 and 2014 and registered in the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record. We described vaccine uptake for representative antigens (pertussis, pneumococcus, measles) by age in days and stratified by ethnicity, region and birth cohort. Alluvial diagrams were used to illustrate common journeys through the vaccination schedule, and we applied survival analysis using accelerated failure time models (AFT) to predict age of vaccine receipt based on timing of previous doses. RESULTS: 573,015 children were followed up until their fifth birthday, when they had 90.16 % coverage for two doses of measles, mumps, rubella (MMR) vaccine and 88.78% coverage for four doses of diphtheria, tetanus, pertussis (DTP) vaccine. Overall, the later the age at which a vaccine was due, the more delay in vaccination. Children of Black Ethnicity or from London showed deviating uptake patterns. If a child received their third DTP dose more than a year later than recommended, they would receive the next dose 2.7 times later than a child who was vaccinated on time. A smaller delay was found for children who did not receive first MMR dose on time. DISCUSSION: We showed that the risk of vaccination delay increased with the age of the child and significant delay of previous doses. Primary care data can help to promptly identify children at higher risk of delayed vaccination.

As the COVID19 pandemic progresses, there is an increasing need to evaluate the performance of vaccine strategies. This study investigated the vaccine schedule performance of heterologous vaccination compared to homologous vaccination in preventing Omicron SARS-CoV2 infection in the adult population. This retrospective cohort study utilized data from the Infections Regional Information System and the Apulia Regional Vaccine Registry to identify individuals who received a booster dose of one of 14 different COVID19 vaccination schedules between September 2021 and August 2022 in the province of Lecce, Southern Italy. The standardized cumulative incidence of SARS-CoV2 infection after the booster dose was assessed and the risk of infection between subgroups of heterologous and homologous vaccination schedules was compared using the Cochran-Mantel-Haenszel test. A total of 469,069 subjects were included in the study. The standardized incidence of SARS-CoV2 infection varied greatly among different vaccine schedules, with the highest and lowest being AZ-AZ-BNT (34.7 %) and MOD-MOD-BNT (18.9 %), respectively, and some heterologous schedules performing better than homologous ones. The risk of SARS-CoV2 infection was significantly lower in individuals who received specific heterologous vaccination schedules compared to homologous vaccination schedules, the best performing being MOD-MOD-BNT with a common odd ratio of 0.661 (IC. 95 % [0.620-0.704]). This study provides evidence that heterologous vaccination schedules may be more effective in preventing Omicron SARS-CoV2 infection compared to homologous vaccination schedules, highlighting how the vaccine product, rather than the platform, is involved in the different protection provided by heterologous vaccination.

The Healthy People 2030 goal is for 80% of all adolescents to complete their HPV vaccination series. Per the 2021, National Immunization Survey-Teen (NIS-Teen), 61.7% of adolescents have completed the series, and Indiana lags below the national average (55.2%). The present study estimated the 2-dose HPV vaccine series completion rates across Indiana counties among individuals aged 9-14 years who received their first dose of vaccine and determined what factors were associated with series completion at the county level. The association of county-level sociodemographic and health measures with series completion was also examined. Data were extracted from the Indiana Immunization Information System (IIS), administered by the Indiana Department of Health. All vaccine providers are required to report all immunizations to the system for any patient under age 19 years. All Indiana children ages 9-14 years at the time of first dose who had initiated HPV vaccination in 2017 or 2018 were included. Two-dose series completion was evaluated through October of 2020, allowing a minimum gap of 22 months from first dose administration. All statistical analyses were conducted at the county-level. The Indiana HPV vaccination series completion rate among individuals that received the first dose was on average 73% across counties, ranging from 55.7% to 90.4%. Higher series completion was positively associated with primary care providers per capita, participation in mammography screening among Medicare enrollees, median household income, life expectancy, percentage of residents with some college, percentage of adults up-to-date with colonoscopy screening, and percentage of adults with flu vaccine. There was wide variability in series completion across Indiana counties. HPV series completion was associated with county-level sociodemographic and health measures, particularly variables reflecting difficulties with access to care and lack of financial resources.

Porcine Reproductive and Respiratory Syndrome (PRRS) is an important viral disease of swine that causes significant mortality in piglets and production losses in adult pigs. In this study, we investigated the protective efficacy of an inactivated PRRS virus vaccine candidate and evaluated the differences in PRRSV specific anamnestic response in piglets when challenged with live PRRSV at two different intervals post-immunization. Six-week-old piglets were immunized intramuscularly with an inactivated, Montanide ISA-206 adjuvanted Indian PRRSV isolate, followed by a booster dose at 21 days post-immunization. Homologous live PRRS virus challenge was done on 60 and 180 days post-booster (dpb). We assessed humoral and cell-mediated immune responses at various intervals post-immunization and after challenge. Viraemia, virus shedding in nasal secretions and lung lesion scores were studied to assess the efficacy of the vaccine candidate. All the immunized pigs developed PRRSV-specific antibodies upon booster dose administration. Neutralizing antibody (NA) titres before challenge, in most animals, ranged between 0 and 4. Potentially protective NA titre of 8 was observed in serum of seven out of the 12 immunized piglets after challenge, across the immunized groups. A significant increase in the mean T-helper, T-cytotoxic, memory or activated T-helper and NK cell populations was observed in immunized piglets challenged at 180 dpb, from 4 to 11 dpc, 5 to 11 dpc, 5 to 7 dpc and 6 to 11 dpc, respectively as compared to the challenge controls. Protective efficacy of the inactivated PRRSV antigen against the homologous virus challenge was evidenced by earlier onset of PRRSV specific virus neutralizing antibodies and cell mediated immune responses, reduced viremia, nasal virus shedding and severity of lung lesions in immunized piglets as compared to unimmunized controls post-challenge. Our results indicated that the inactivated PRRSV antigen elicited better virus specific anamnestic immune responses in piglets when challenged at six months after the single booster dose, due to age related increase in antigen-specific memory T helper cell responses, as compared to those challenged at 2 months post booster.

INTRODUCTION: The struggle against influenza, and more recently against Coronavirus Disease 2019 (COVID-19), relies mostly on protective measures and vaccines. In France, COVID-19 vaccination campaigns include children over 5 years of age, whereas the influenza vaccine is reserved for children and infants older than 6 months with severe chronic disease. The final decision to vaccinate ultimately rests with the parents. This study aimed to explore the opinions of parents regarding COVID-19 and influenza vaccinations, and which factors are likely to influence their decision in order to improve prevention approaches, and thus obtain better vaccination coverage among children. METHODS AND SURVEY: In this trans-sectional multicenter survey, self-administered questionnaires were sent to parents of children attending 14 childcare institutions over a period of 2 months, December 2021-February 2022. The questionnaire consisted of three sections: the first collected general, social and professional data, the second addressed perceived parental acceptability regarding influenza and COVID-19 vaccinations in healthy children, while the last section explored the main sources of information consulted by the parents regarding vaccinations. Subject's characteristics were described using number and percentages, as they are all categorical variables. Description of answers regarding both influenza and COVID-19 sources of information data were performed. Characteristics of patients answers were described and compared according to intention of vaccine groups. RESULTS: Among the 343 questionnaires collected, 41.7 % of respondents stated they were supportive of vaccination of their children against influenza and 37 % against COVID-19. Media (Internet, TV and radio) were the most cited sources of information. Incentive factors for both vaccination against influenza and COVID-19 were individual, and collective protection. Limiting factors were fear of side effect and Age of the child. Media was the sole source of information, concerning vaccination against influenza for 59 % non-graduates and 28 % of participants having a higher education level, and respectively 49 % and 19 % for vaccination against COVID-19. The acceptability rate was influenced by the level of education and the sources of information. DISCUSSION AND CONCLUSION: About 40 % of the parents were supportive of children's vaccinations against COVID-19 and influenza respectively (37 % and 42 %) in order to protect the vulnerable people around them. The media influences the decision to vaccinate especially when the level of education is low.

INTRODUCTION: Timeliness of routine vaccination shapes childhood infection risk and thus is an important public health metric. Estimates of indicators of the timeliness of vaccination are usually produced at the national or regional level, which may conceal epidemiologically relevant local heterogeneities and makeitdifficultto identify pockets of vulnerabilities that could benefit from targeted interventions. Here, we demonstrate the utility of geospatial modelling techniques in generating high-resolution maps of the prevalence of delayed childhood vaccination in The Gambia. To guide local immunisation policy and prioritize key interventions, we also identified the districts with a combination of high estimated prevalence and a significant population of affected infants. METHODS: We used the birth dose of the hepatitis-B vaccine (HepB0), third-dose of the pentavalent vaccine (PENTA3), and the first dose of measles-containing vaccine (MCV1) as examples to map delayed vaccination nationally at a resolution of 1 × 1-km2 pixel. We utilized cluster-level childhood vaccination data from The Gambia 2019-20 Demographic and Health Survey. We adopted a fully Bayesian geostatistical model incorporating publicly available geospatial covariates to aid predictive accuracy. The model was implemented using the integrated nested Laplace approximation-stochastic partial differential equation (INLA-SPDE) approach. RESULTS: We found significant subnational heterogeneity in delayed HepB0, PENTA3 and MCV1 vaccinations. Specificdistricts in the central and eastern regions of The Gambia consistentlyexhibited the highest prevalence of delayed vaccination, while the coastal districts showed alower prevalence forallthree vaccines. We also found that districts in the eastern, central, as well as in coastal parts of The Gambia had a combination of high estimated prevalence of delayed HepB0, PENTA3 and MCV1 and a significant population of affected infants. CONCLUSIONS: Our approach provides decision-makers with a valuable tool to better understand local patterns of untimely childhood vaccination and identify districts where strengthening vaccine delivery systems could have the greatest impact.

FMD remains endemic in many Asian and African countries where multiple variants of serotypes O and A, among others, currently circulate. Due to lack of cross-protection between serotypes and incomplete protection between some strains even within a serotype, an important challenge for the application of effective vaccination programs is to select highly immunogenic and widely cross-reactive vaccine strains. Adaptation of a candidate field virus for use as a vaccine can be quite complex, so that whenever possible, the use of well-established vaccine viruses could have enormous advantages. FMD vaccine strains harmonized for use in South America have shown excellent results in FMD control, not only in the region, where it is still used systematically as a preventive measure, but also more recently in some Asian countries. To gain further insight into the immunogenic spectrum of these strains, VN tests (VNT) were performed with sera from cattle and/or pigs vaccinated with monovalent (type O) or trivalent (types O and A) formulations against 122 type O and 32 type A field viruses isolated from 35 countries in Asia and Africa, belonging to different lineages. Almost all VNT titers obtained were within the expected protective level, indicating the wide immunogenic spectrum of high potency FMD vaccines formulated with O1 Campos, A24 Cruzeiro and A Argentina 2001 South American vaccine strains belonging to EURO-SA topotypes against currently active viruses from other topotypes. These in vitro results are in line with previously reported in vivo challenge tests in pigs against three A/ASIA/Sea-97 isolates and two isolates belonging to type O lineages O/SEA/Mya-98 and O/ME-SA/Ind-2001e.

INTRODUCTION: Immunization Information Systems (IIS) play an important information-sharing role at the point of care, and provide vital vaccination data for research studies and policy-makers. Previous validation studies comparing the accuracy of state registry data to health records have had mixed results. METHODS: We conducted a retrospective review of EHR vaccination data for 9-17 year-old patients from 10 Oregon primary care clinics who had at least one ambulatory care visit in the past 3 years from the date of validation data collection. Data on 100 age eligible youth were captured per clinic. We compared HPV and Tdap vaccinations captured in the EHR to the Oregon ALERT IIS. All clinics were located in rural areas with both family medicine (n = 7) and pediatric (n = 3) primary care clinics. RESULTS: Overall agreement for HPV vaccination between EHR and ALERT IIS was 89.4 % (k = 0.83; p < 0.05). For Tdap vaccination overall agreement was 80.8 % (k = 0.60; p < 0.05). Pediatric clinics showed a higher overall vaccine agreement for both HPV at 93.3 % (k = 0.89; p < 0.05) and Tdap at 95.3 % (k = 0.90; p < 0.05). Among clinics that used bidirectional data exchange (only family medicine clinics), HPV agreement was higher at 91 % (k = 0.85) versus 88 % (k = 0.81; p < 0.05) and was lower for Tdap 75 % with bidirectional data exchange (k = 0.50) versus 86 % without bidirectional data exchange (k = 0.70; p < 0.05). When the EHR and ALERT IIS disagreed, ALERT ISS usually had additional vaccines. CONCLUSIONS: ALERT IIS data provides more accurate data than EHRs can provide when measuring vaccine delivery among adolescents in rural Oregon.

INTRODUCTION: Worldwide, tetanus-diphtheria-acellular pertussis (Tdap) vaccination coverage of healthcare professionals (HCPs) is below 40%, but this data is not available for Brazil. We hypothesize that a high number of HCPs are not immune to pertussis in Brazil. Main objective was to determine the seroprevalence of anti-pertussis toxin (anti-PT IgG) among HCPs. Secondary objectives were to evaluate Tdap vaccination coverage, to assess predictive factors associated with anti-PT IgG, and to estimate the decay of anti-PT IgG and time to Tdap vaccination. METHODS: Observational cross-sectional serological study in 352 HCPs who worked at São Paulo Hospital - Federal University of São Paulo (UNIFESP) in 2020, approved by UNIFESP Ethics Committee. Data collected included sociodemographics, knowledge about Tdap, and vaccination status. Anti-PT IgG were quantified by ELISA: <10 IU/mL seronegative and ≥ 10-1000 IU/mL seropositive. Titers ≥ 10-50 IU/mL were classified low positivity, indicating no recent B. pertussis infection or Tdap vaccination; >50 IU/mL high positivity, indicating recent B. pertussis infection or Tdap vaccination, and > 100 IU/mL as acute B. pertussis infection or Tdap vaccination in the previous year. Comparisons were done by Chi-square test, multivariable logistic regression, and Pearsońs correlation, at 5% p-level. RESULTS: 331/352 HCPs were not aware the Brazilian National Immunization Program recommends Tdap for all HCPs and pregnant women. 68/339 HCPs received Tdap (mean 3.1 ± 2.0 years). 55/352 were seronegative for pertussis, all unvaccinated. 56/271 with no history of Tdap vaccination had high positivity. The probability of anti-PT IgG > 50 IU/mL was 11.5 times higher in Tdap vaccinated HCPs than in non-vaccinated (p < 0.001). There was a weak but significant correlation between anti-PT IgG and interval of Tdap vaccination (r = 0.404; p = 0.001). Anti-PT IgG dropped 5 IU/mL/year (p = 0.001). CONCLUSION: Better education of HCPs on needs and benefits of Tdap vaccination is critical. Goals must be to improve HCPs vaccination coverage.

BACKGROUND: Although CoronaVac was the only Covid-19 vaccine adopted in the first months of the Brazilian vaccination campaign, randomized clinical trials to evaluate its efficacy in elderly adults were limited. In this study, we use routinely collected surveillance and SARS-CoV-2 vaccination and testing data comprising the population of the fifth largest city of Brazil to evaluate the effectiveness of CoronaVac in adults 60+ years old against severe outcomes. METHODS: Using large observational databases on vaccination and surveillance data from the city of Fortaleza, Brazil, we defined a retrospective cohort including 324,302 eligible adults aged ≥60 years to evaluate the effectiveness of the CoronaVac vaccine. The cohort included individuals vaccinated between January 21, 2021, and August 31, 2021, who were matched with unvaccinated persons at the time of rollout following a 1:1 ratio according to baseline covariates of age, sex, and Human Development Index of the neighborhood of residence. Only Covid-19-related severe outcomes were included in the analysis: hospitalization, ICU admission, and death. Vaccine effectiveness for each outcome was calculated by using the risk ratio between the two groups, with the risk obtained by the Kaplan-Meier estimator. RESULTS: We obtained 62,643 matched pairs for assessing the effectiveness of the two-dose regimen of CoronaVac. The demographic profile of the matched population was statistically representative of the population of Fortaleza. Using the cumulative incidence as the risk associated with each group, starting at day 14 since the receipt of the second dose, we found an 82.3 % (95 % CI 66.3-93.9) effectiveness against Covid-19-related death, 68.4 % (95 % CI 42.3-86.4) against ICU admission, and 55.8 % (95 % CI 42.7-68.3) against hospital admission. CONCLUSIONS: Our results show that, despite critical delays in vaccine delivery and limited evidence in efficacy trial estimates, CoronaVac contributed to preventing deaths and severe morbidity due to Covid-19 in elderly adults.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of livestock which is prevalent across Africa, the Middle East, Asia, and South America where it has a severe economic impact on the agriculture industry. Vaccination with inactivated viral vaccines is used as the main control measure in these endemic regions of the world, however the presence of multiple serotypes, subtypes, and the continual emergence of new, antigenically divergent strains limits its effectiveness. East Africa (EA) has been identified as a region that would particularly benefit from updated FMD vaccines, since those currently in use contain older strains which do not provide good protection against contemporary strains. Four serotypes are currently circulating in EA, necessitating the development of a quadrivalent vaccine containing representative strains of each serotype. A key consideration in the selection of vaccine strains is the stability of the virus particle, since the capsids readily dissociate on exposure to elevated temperatures, but only intact capsids induce protective immunity to FMD. Therefore, with a view to producing a more stable, updated quadrivalent vaccine for EA, we recently screened a panel of foot-and-mouth disease virus (FMDV) isolates from the region to select strains with naturally higher thermostabilities and confirmed their immunogenicity in cattle. Herein we describe the formulation and serological assessment of wild-type and recombinant quadrivalent vaccine candidates comprising these stable strains, and demonstrate that both vaccines generate high neutralising antibody titres against the homologous strains and also to heterologous strains from EA. Importantly, the vaccine passed the criteria set by the AgResults vaccine challenge project and offers good cross-protection against a panel of regional FMDV strains.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring. METHODS: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios. RESULTS: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19. CONCLUSION: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

BACKGROUND: An approach to a preventive HIV vaccine is induction of effective broadly neutralizing antibodies (bnAbs) and effector binding antibodies (bAbs). Preclinical studies suggest that trimeric envelope (Env) proteins may elicit nAbs, which led to the development of the recombinant gp145 subtype C Env protein (gp145 C.6980) immunogen. HVTN 122 was a Phase 1 trial that evaluated the safety, tolerability, and immunogenicity of gp145 C.6980 in adults. METHODS: Healthy, HIV-1 seronegative adults received three intramuscular injections of gp145 C.6980 with aluminum hydroxide (alum) at months 0, 2, and 6 at either 300 mcg (high dose, n = 25) or 100 mcg (low dose, n = 15), or placebo/saline (placebo, n = 5). Participants were followed for 12 months. RESULTS: Forty-five participants were enrolled. High and low doses of the study protein were well-tolerated, with mild or moderate reactogenicity commonly reported. Only one adverse event (mild injection site pruritis) in one participant (low dose) was considered product-related; there were no dose-limiting toxicities. High and low dose recipients demonstrated robust bAb responses to vaccine-matched consensus gp140 Env and subtype-matched gp120 Env proteins two weeks post-last vaccination (response rates >90 %), while no responses were detected to a heterologous subtype-matched V1V2 antigen. No significant differences were seen between high and low dose groups. Participants in both experimental arms demonstrated nAb response rates of 76.5 % to a tier 1 virus (MW9635.26), but no responses to tier 2 isolates. Env-specific CD4 + T-cell responses were elicited in 36.4 % of vaccine recipients, without significant differences between groups; no participants demonstrated CD8 + T-cell responses. CONCLUSIONS: Three doses of novel subtype C gp145 Env protein with alum were safe and well-tolerated. Participants demonstrated bAb, Env-specific CD4 + T-cell, and tier 1 nAb responses, but the regimen failed to induce tier 2 or heterologous nAb responses. CLINICAL TRIALS REGISTRATION: NCT03382418.

OBJECTIVE: We carried out a study to estimate the vaccine effectiveness (VE) of homologous vaccination schedules against COVID-19, using data from mandatory information systems from Bogota, Colombia. METHODS: A test-negative case-control study in adults from Bogota (Colombia), between March 1st of 2021 and February 25th of 2022. We assess VE among symptomatic COVID-19 cases during the Mul, Delta, and Omicron predominance periods in Bogota, with controls matched by sex, age (±5 years), and date of testing (±7 days), using a case:control ratio of 1:1. We selected homologous vaccination schedules with ChAdOx1, CoronaVac, BNT162b2, mRNA-1273, and Ad26.COV2.S. VE was reported as one minus the odds ratio in adjusted conditional logistic regressions, with their 95% confidence intervals (CI). A p-value < 0.05 was considered statistically significant. RESULTS: 52,913 cases were matched to controls, 16,722 for Mu, 14,094 for Delta, and 22,097 for Omicron. VE was high against COVID-19 during Mu weeks with full vaccination using the monovalent BNT162b2 (VE: 69; 95% CI, 65 to 72) vaccine and ChAdOx1 (VE: 64; 95% CI, 31 to 81) and significantly lower with CoronaVac (P < 0.001) and Ad26.COV2.S (P = 0.005). During Delta, VE against COVID-19 was higher with BNT162b2 (VE: 55; 95% CI, 51 to 58). The VE for COVID-19 cases during Omicron was higher with a booster dose of monovalent BNT162b2 (VE: 45; 95% CI, 34 to 54). The VE of primary series and booster for ChAdOx1, Ad26.COV2.S, and CoronaVac did not show protection for Omicron. CONCLUSION: Our study provides further evidence on the protective effect of mRNA vaccines for Omicron, and warrant that the duration of protection against symptomatic infection may last for only a few months.

How do citizens choose COVID-19 vaccines, and when do they wish to be vaccinated? A choice-based conjoint experiment was conducted in Hong Kong to examine factors that shape citizens' preference toward COVID-19 vaccines and their time preference to be vaccinated, which is overlooked in extant literature. Results suggest people are most concerned about vaccines' efficacy and severe side-effects, and that cash incentives are not useful in enhancing vaccine appeal. The majority of respondents show low intention for immediate vaccination, and many of them want to delay their vaccination. Further analysis shows that their time preference is shaped more by respondent characteristics than vaccine attributes. In particular, confidence in the vaccine, trust in government, and working in high-risk professions are associated with earlier timing for vaccine uptake. Meanwhile, forced COVID testing would delay vaccination. The findings offer a novel view in understanding how people decide whether and when to receive new vaccines, which have pivotal implications for a head start of any mass vaccination programs.

Barriers and enablers to vaccination of care home (CH) staff should be identified in order to develop interventions to address them that increase uptake and protect residents. We aimed to synthesis the evidence describing the barriers and enablers that affect the influenza vaccination uptake of care home (CH) staff. METHOD: We searched PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, AMED, IBSS, SCOPUS to identify quantitative, qualitative or mixed-method studies. Data related to health or social care workers in CHs reported barriers or enablers were extracted and mapped to the Theoretical Domains Framework (TDF); the data within each domain were grouped and categorized into key factors affecting influenza vaccine uptake among CH staff. RESULTS: We screened 4025 studies; 42 studies met our inclusion criteria. Thirty-four (81 %) were surveys. Five theoretical domains were frequently reported as mediators of influenza vaccine uptake: Beliefs about consequences (32 studies), Environmental context and resources (30 studies), Emotions (26 studies), Social influences (25 studies), Knowledge (22 studies). The low acceptance rate of the influenza vaccine among CH staff can be attributed to multiple factors, including insufficient understanding of the vaccine, its efficacy, or misconceptions about the vaccine (knowledge), perceiving the vaccine as ineffective and unsafe (beliefs about consequences), fear of influenza vaccine and its side effects (emotions), and experiencing limited accessibility to the vaccine (environmental context and resources). CONCLUSION: Interventions aimed at increasing influenza vaccine uptake among CH staff should focus on addressing the barriers identified in this review. These interventions should include components such as enhancing knowledge by providing accurate information about vaccine benefits and safety, addressing negative beliefs by challenging misconceptions, managing concerns and fears through open communication, and improving accessibility to the vaccine through convenient on-site options. This review provides a foundation for the development of tailored Interventions to improve influenza vaccine uptake among CH staff.

SARS-CoV-2 serological studies suggest that individual serum antibody repertoires can affect neutralisation breadth. Herein, we asked whether a BNT162b2 vaccine-induced epitope dominance pattern (i.e., predominant viral structural domain targeted by serum antibodies for virus neutralisation) affects cross-variant neutralisation. When a neutralisation assay against the ancestral strain was carried out using 16 vaccine sera preabsorbed with a recombinant receptor-binding domain (RBD) or an N-terminal domain (NTD) protein, three and 13 sera, respectively, showed lower neutralisation under NTD and RBD protein-preabsorbed conditions than under the other protein-preabsorbed conditions. This suggests that the NTD was responsible for virus neutralisation in three sera, whereas the other 13 sera elicited RBD-dominant neutralisation. The results also suggest the presence of infectivity-enhancing antibodies in four out of the 13 RBD-dominant sera. A neutralisation assay using SARS-CoV-2 variants revealed that NTD-dominant sera showed significantly reduced neutralising activity against the B.1.617.2 variant, whereas RBD-dominant sera retained neutralising activity even in the presence of infectivity-enhancing antibodies. Taken together, these results suggest the followings: (i) epitope dominance patterns are divided into at least two types: NTD-dominant and RBD-dominant; (ii) NTD-dominant sera have less potential to neutralise the B.1.617.2 variant than RBD-dominant sera; and (iii) infectivity-enhancing antibodies play a limited role in cross-variant neutralisation against the five variants tested.

BACKGROUND: This study describes the evolution of vaccination acceptability and associated determinants in the French general population between 2000 and 2021, and vaccinations with the highest vaccine hesitancy between 2010 and 2021. METHODS: Data were collected from the nine national 'Health Barometer' cross-sectional surveys conducted between 2000 and 2021. These surveys included French-speaking individuals aged 18-75 years old who were selected through randomly generated landline and mobile phone numbers. Participants were asked about their acceptability of vaccination in general and their vaccine hesitancy toward any particular vaccinations. Determinants of vaccination acceptability were studied using univariate and multivariate Poisson regressions. RESULTS: The proportion of persons who found vaccination acceptable in general (i.e., answering "very" or "somewhat" favourable in the survey interview) decreased from 91.1% in 2000 to 61.2% in 2010 (the latter year coinciding with the 2009 H1N1 influenza pandemic), increased in 2014 (78.8%), slightly fluctuated until 2019 (74.2%), and increased again in both 2020 (80.0%) and 2021 (82.5%) during the COVID-19 pandemic. Irrespective of the year, acceptability was higher among persons with higher incomes, those with a higher education level, and individuals not living alone. In 2021, for the first time, vaccination acceptability was higher among persons over 44 years old (versus 18-24 year-olds) and among retired persons (versus workers). The highest hesitancy rate for a vaccine was for the 2009 H1N1 influenza virus in 2010 (41% answering "somewhat" or "very" unfavourable). In 2021, the highest rate was for the COVID-19 vaccine (21%). DISCUSSION: Unlike the experience of the 2009 AH1N1 influenza pandemic, which led to a collapse in vaccination acceptability among the French general population, acceptability continued to increase during the COVID-19 pandemic. However, the pre-2010 level was not reached. Our results show a tendency towards a widening social and economic gap in terms of vaccine acceptability over time.

BACKGROUND: Hepatitis B virus (HBV) infection is endemic in West Africa. There has been a significant increase in the Bronx West African (WA) community. To achieve HBV elimination, vaccination of non-immune individuals is important. Unfortunately, vaccine uptake in immigrant populations is at this time very limited. METHODS: An educational program was conducted by medical providers of WA origin in collaboration with local faith-based organizations, after which free HBV screening was offered. Non-immune individuals were initially recommended to contact their medical provider or referred to the Department of Health for vaccination. Beginning in 2021, the program offered vaccination. A questionnaire including reasons for vaccination in the program was offered. FINDINGS: Among the first500 individuals screened,34.6 % required vaccination. Among those screened before program vaccine availability, 72.2 % initiated the vaccination series,with38.2 % obtainingit at an outside setting and34 % returning when available through the program.Among patients screened after program vaccineavailability, 92.1 % initiated the series.Of those receiving vaccination in the program and completing the questionnaire,70.7 % had access to care but chose vaccination by the program because of the trust instilled by WA personnel. INTERPRETATION: Our findings demonstrate the effectiveness of integrating vaccination into an HBV screening program for an immigrant population. It emphasizes the importance of timeliness and cultural sensitivity.

BACKGROUND: Reducing the spread of infectious diseases through vaccination faces the challenge of vaccine hesitancy: referring to questions, concerns and doubts arising when making a vaccine-related decision. A motivational state often arising within people exposed to health messages supporting informed decision making is psychological reactance, functioning as a driver to behavior opposed to the one recommended through the health message. Hence, there is a pressing need for communication strategies effective in counteracting reactance to health messages. METHODS: This study tested two communication strategies that can potentially reduce psychological reactance and ameliorate evaluations of the message and subsequent behavioral vaccination intentions in the context of COVID-19. These were: (1) explicitly reminding individuals of their freedom of choice (to either accept or refuse the vaccine) and (2) providing a two-sided message, including, apart from evidence-based information on the necessity of vaccines, a set of concerns, and questions (about the vaccines) which are refuted immediately. A total of 234 participants who indicated having concerns about the COVID-19 vaccine participated in a 2 (freedom of choice: no choice vs. choice) × 2 (message sidedness: one-sided vs. two-sided) between-subjects online experiment where they received an informational brochure about COVID-19 vaccination. RESULTS: The results show that emphasizing freedom of choice significantly increased perceived credibility of the message, perceived information utility, and ultimately, vaccination intentions. A decrease in psychological reactance mediated these effects. Message sidedness did only show a significant direct effect on perceived information utility. No interaction effect was found. CONCLUSION: These findings indicate the importance of freedom of choice in reducing psychological reactance, which in its turn can lead to an increase of positive message evaluations and vaccination intentions among individuals who express concerns. The opportunities of message sidedness as an efficacious vaccination communication strategy should be further investigated.

Interference with the normal synthesis of LPS was shown to enhance immune responses to conserved outer membrane proteins. In the present study, we have constructed three vaccine candidates by deleting four genes (rfaL, rfbB, rffG and wzy) associated with LPS synthesis in the wild-type strain UK-1. Virulence assessment showed that after oral immunization of BALB/c mice, all mutant strains were attenuated and had significantly reduced ability to colonize host tissues compared to the wild-type strain. In addition, all three vaccine candidates induced elevated humoral, mucosal and cellular immune responses against S. Typhimurium and S. Choleraesuis OMPs compared to the PBS-treated group. Finally, immunization of mice with the rSC0136 vaccine candidate strain provided 100 % and 40 % protection against S. Typhimurium and S. Choleraesuis challenge, respectively. These results suggest that the deletion of LPS synthesis-related genes may be an effective strategy against homologous serotypes, but provides only partial protection against heterologous serotypes.

BACKGROUND: Vaccinations against SARS-CoV-2 have consistently been shown to reduce the risk of severe COVID-19 disease. However, uptake of boosters has stalled in the United States at less than 20% of the eligible population. The objective of this study was to assess the reasons for not having obtained a bivalent booster within an existing COVID-19 cohort. METHODS: A total of 2196 adult participants from the Arizona CoVHORT, a population-based cohort in the United States established in May 2020, who had received at least one dose of the COVID-19 vaccine, responded to surveys administered between February 13 and March 29, 2023 querying receipt of a bivalent booster and if not, the reasons for not receiving it. Descriptive statistics were employed, including frequencies of responses by participant characteristics, and multivariable logistic regression was used to assess the association between participant characteristics and selected themes for not having received the bivalent booster. RESULTS: The most commonly reported reason for not having been boosted was a prior SARS-CoV-2 infection (39.5%), followed by concern about vaccine side effects (31.5%), believing that the booster would not provide additional protection over the vaccines already received (28.6%), and concern about booster safety (23.4%) or that it would not protect from SARS-CoV-2 infection (23.1%). For themes related to reasons for not having been boosted, those 60 years of age or older were less likely to select items related to knowledge (OR: 0.24; 95% CI: 0.11-0.55) or logistical concerns (OR: 0.09; 95% CI: 0.03-0.30) about the vaccine; while those reporting Hispanic ethnicity were more likely to convey concerns about logistics than those reporting non-Hispanic ethnicity (OR: 2.15; 95% CI: 1.08-4.30). Finally, compared to college graduates, those with some college or technical school were significantly more likely to select items related to the risks and benefits of the bivalent vaccine not being clear as reasons for not having been boosted (OR: 2.41; 95% CI: 1.69-3.43). CONCLUSIONS: Improvement in booster uptake is necessary for optimal public health in the United States. The development of vaccines against SARS-CoV-2 occurred at an unprecedented speed, but vaccine uptake remains among the greatest current public health challenges as updated boosters continue to be developed and made available to the public. Interventions to improve vaccination rates require a variety of approaches.

OBJECTIVES: Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. METHODS: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. RESULTS: Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]). CONCLUSION: Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.

Shigella species cause severe disease among travelers to, and children living in, endemic countries. Although significant efforts have been made to improve sanitation, increased antibiotic resistance and other factors suggest an effective vaccine is a critical need. Artificial Invaplex (InvaplexAR) is a subunit vaccine approach complexing Shigella LPS with invasion plasmid antigens. In pre-clinical studies, the InvaplexAR vaccine demonstrated increased immunogenicity as compared to the first generation product and was subsequently manufactured under cGMP for clinical testing in a first-in-human Phase 1 study. The primary objective of this study was the safety of S. flexneri 2a InvaplexAR given by intranasal (IN) immunization (without adjuvant) in a single-center, open-label, dose-escalating Phase 1 trial and secondarily to assess immunogenicity to identify a dose of InvaplexAR for subsequent clinical evaluations. Subjects received three IN immunizations of InvaplexAR, two weeks apart, in increasing dose cohorts (10 µg, 50 µg, 250 µg, and 500 μg). Adverse events were monitored using symptom surveillance, memory aids, and targeted physical exams. Samples were collected throughout the study to investigate vaccine-induced systemic and mucosal immune responses. There were no adverse events that met vaccination-stopping criteria. The majority (96%) of vaccine-related adverse events were mild in severity (most commonly nasal congestion, rhinorrhea, and post-nasal drip). Vaccination with InvaplexAR induced anti-LPS serum IgG responses and anti-Invaplex IgA and IgG antibody secreting cell (ASC) responses at vaccine doses ≥250 µg. Additionally, mucosal immune responses and functional antibody responses were seen from the serum bactericidal assay measurements. Notably, the responder rates and the kinetics of ASCs and antibody lymphocyte secretion (ALS) were similar, suggesting that either assay may be employed to identify IgG and IgA secreting cells. Further studies with InvaplexAR will evaluate alternative immunization routes, vaccination schedules and formulations to further optimize immunogenicity. (Clinical Trial Registry Number NCT02445963).

OBJECTIVE: To understand COVID-19 vaccine decision-making among Black women in the United States. METHODS: We conducted qualitative interviews with 60 Black women (both African American and first- and second-generation immigrants originating from Africa and the Caribbean) living in the Minneapolis/St. Paul Metropolitan Area. RESULTS: Participants who were highly motivated to get vaccinated described their trust in science and a desire to protect themselves and those around them; while those who delayed vaccination reported doubts about vaccine safety. Many reported being influenced by targeted misinformation including the pervasive vaccine myths related to reproductive health. Historical trauma from unethical biomedical research and experiences of racism were also motivating factors. There were several concerns raised that were specific to ethnic groups. CONCLUSIONS: Current public health strategies that are intended to promote COVID vaccination are failing Black communities. Participants highlighted the need for clear and culturally appropriate communication about COVID-19 and the vaccines that is aligned with their communities' values and addresses misinformation. The critical insights we have gained by listening to these communities should be used to develop novel vaccination policy approaches.

The M protein of group A streptococci (Strep A) is a major virulence determinant and protective antigen. The N-terminal region of the M protein is variable in sequence, defines the M/emm type, and contains epitopes that elicit opsonic antibodies that protect animals from challenge infections. Although there are >200 M types of Strep A, there is now evidence that structurally related M proteins can be grouped into clusters and that immunity may be cluster-specific in addition to M type-specific. This observation has led to recent studies of structure-based design of multivalent M peptide vaccines to select peptides predicted to cross-react with heterologous M types to improve vaccine coverage. In the current study, we have applied a refined series of peptide structural algorithms to predict immunological cross-reactivity among 117 N-terminal M peptides representing the most prevalent M types of Strep A. Based on the results of the structural analyses, in combination with global M type prevalence data, we constructed a 32-valent vaccine containing 19 cross-reactive vaccine candidates predicted to cross-react with 37 heterologous M peptides to which were added 13 type-specific M peptides. The 4-protein recombinant vaccine was immunogenic in rabbits and elicited significant levels of antibodies against 31/32 (97%) vaccine peptides and 28/37 (76%) peptides predicted to cross-react. The vaccine antisera also promoted opsonophagocytic killing of vaccine and cross-reactive M types of Strep A. Based on a recent analysis of M type prevalence of Strep A, the potential global coverage of the 32-valent vaccine is ∼90%, ranging from 68% in Africa to 95% in North America. Our results indicate the utility of structure-based design that may be applied to future studies of broadly protective M peptide vaccines.

BACKGROUND: Vaccination continues to be the key public health measure for preventing severe COVID-19 outcomes. Certain groups may be at higher risk of incomplete vaccine schedule, which may leave them vulnerable to COVID-19 hospitalisation and death. AIM: To identify the sociodemographic and clinical predictors for not receiving a scheduled COVID-19 vaccine after previously receiving one. METHODS: We conducted two retrospective cohort studies with ≥3.7 million adults aged ≥18 years in Scotland. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) of not receiving a second, and separately a third dose between December 2020 and May 2022. Independent variables included sociodemographic and clinical factors. RESULTS: Of 3,826,797 people in the study population who received one dose, 3,732,596 (97.5%) received two doses, and 3,263,153 (86.5%) received all doses available during the study period. The most strongly associated predictors for not receiving the second dose were: being aged 18-29 (reference: 50-59 years; aOR:4.26; 95% confidence interval (CI):4.14-4.37); hospitalisation due to a potential vaccine related adverse event of special interest (AESI) (reference: not having a potential AESI, aOR:3.78; 95%CI: 3.29-4.35); and living in the most deprived quintile (reference: least deprived quintile, aOR:3.24; 95%CI: 3.16-3.32). The most strongly associated predictors for not receiving the third dose were: being 18-29 (reference: 50-59 years aOR:4.44; 95%CI: 4.38-4.49), living in the most deprived quintile (reference: least deprived quintile aOR:2.56; 95%CI: 2.53-2.59), and Black, Caribbean, or African ethnicity (reference: White ethnicity aOR:2.38; 95%CI: 2.30-2.46). Pregnancy, previous vaccination with mRNA-1273, smoking history, individual and household severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, and having an unvaccinated adult in the household were also associated with incomplete vaccine schedule. CONCLUSION: We observed several risk factors that predict incomplete COVID-19 vaccination schedule. Vaccination programmes must take immediate action to ensure maximum uptake, particularly for populations vulnerable to severe COVID-19 outcomes.

INTRODUCTION: Since vaccination adherence is crucial in reducing morbidity and mortality during a pandemic, we characterized the association between demographic, intelligence, and personal attributes and COVID-19 vaccination adherence among young adults. METHODS: Cohort study including vaccination data of 185,061 personnel, collected during 13 months of COVID-19 vaccination campaign, while a wide array of vaccination incentives were offered. The effect of demographic data (age, gender and socioeconomic status), military medical fitness - fit for combat service, administrative service, or unfit (volunteering), general intelligence score (GIS) and military social score (MSS) assessing social abilities, on vaccine adherence (allocating by IMOH guidelines) was examined. RESULTS: Adherent (vs. nonadherent) personnel presented higher GIS (mean 5.68 ± 1.84 vs. 4.72 ± 1.91) and MSS (median 26 (IQR 23-29) vs. 24 (IQR 19-26)), p < 0.001 for both. Higher intelligence was the strongest predictor for vaccine adherence (OR = 5.38, 95 %CI 5.11-5.67, p < 0.001). The probability for vaccine adherence increased in association with escalating GIS scores, with highest GIS females more likely to adhere to vaccination than same-level males (OR = 5.66, 95 %CI 5.09-6.28 vs. OR = 3.69, 95 %CI 3.45-3.94, respectively, p < 0.001 for both). Medically fit service-members were approximately three times as likely to be adherent than volunteering personnel (OR = 2.90 (95 %CI 2.65-3.17) for administrative and OR = 2.94 (95 %CI 2.70-3.21) for combative fitness, p < 0.001 for both). CONCLUSIONS: During a COVID-19 vaccination campaign, addressing vaccine hesitancy contributing factors and providing wide vaccine availability, GIS and physical fitness had the strongest association with vaccination adherence among young adults. When planning future vaccination campaigns, implementing these insights should be considered to improve adherence.

BACKGROUND: Immunisation during pregnancy with a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine can protect infants against pertussis between birth and paediatric vaccination. We aimed to estimate the vaccine effectiveness (VE) of third-trimester pregnancy immunisation with the three-component acellular pertussis (Td3ap) vaccine at preventing pertussis in infants <2 months in the United States (US), to support a label update. METHODS: We performed a post-hoc sub-analysis of a case-control study conducted in six US Emerging Infections Program Network states between 2011 and 2014. Our analysis included only cases and controls whose mothers were either vaccinated with Td3ap or did not receive any Tdap vaccine. The association between Td3ap maternal immunisation and pertussis in infants was assessed for US data using a frequentist method with conditional logistic regression. A robustified analysis was conducted using Bayesian dynamic borrowing of non-US data, considering a mixing-weighted prior of 90% for historical non-US VE data, and of 10% for a vague prior. VE was estimated as (1-odds ratio) × 100%. Sensitivity analyses accounting for the impact of each non-US study, different mixing weights and missing/ambiguous data were performed. RESULTS: We included 108 cases and 183 controls. Based on US data, the estimated VE of third-trimester maternal immunisation with Td3ap at preventing pertussis in infants <2 months was 78.0% (95% confidence interval: -38.0; 96.5). VE estimated by Bayesian dynamic borrowing of non-US data (with a 90% weight for historical data) was 83.4% (95% credible interval: 55.7; 92.5); sensitivity analyses produced similar VE estimates. CONCLUSIONS: Effectiveness of third-trimester pregnancy immunisation with Td3ap at preventing infant pertussis in the US is very likely to be ≥ 50% and is most likely ∼ 80%. Bayesian dynamic borrowing of non-US VE data allowed overcoming the limited power (due to small sample size) of a brand-specific sub-analysis by considering additional evidence.

BACKGROUND: The immune protection from infection may wane over time as neutralizing antibody levels decline. We aimed to develop a nomogram to predict long-term immune persistence induced by two-dose BBIBP-CorV vaccine and calculate the neutralizing antibody decline probability of individuals. METHODS: In the initial study, a total of 809 participants were recruited and randomly allocated (1:1:1) to vaccination group with three two-dose schedules on days 0 and 14, 0 and 21, or 0 and 28. The participants with neutralizing antibody titers of 16 or above on day 28 after the second dose were followed up at month 3, 6 and 10. Multivariable Cox proportional hazards regression model and nomogram model were used to identify predictors associated with maintaining of neutralizing antibody levels during 10 months after the second dose. RESULTS: A total of 744 participants followed up at day 28 after the second dose. The participants with age ≥ 50 (aHR = 3.556, 95 %CI: 1.141-4.884, P = 0.028) were associated with a high risk of response loss (titers < 16). The participants who were in 0-28 d group (aHR = 0.403, 95 %CI: 0.177-0.919, P = 0.031), had an influenza vaccination history (aHR = 0.468, 95 %CI: 0.267-0.921, P = 0.033) or were female (aHR = 0.542, 95 %CI: 0.269-0.935, P = 0.035) tended to maintain immune persistence during 10 months after the second dose. The nomogram was constructed and showed moderate discrimination[C-index:0.711 (95 %CI: 0.652-0.770); AUC: 0.731 (95 %CI: 0.663-0.792)] and good calibration. CONCLUSIONS: From 28 days to 10 months after receipt of the second dose of the BBIBP-CorV vaccine, neutralizing antibody levels were substantially decreased, especially among men, among persons 50 years of age or older, among persons with the 0-14 d group, and among persons without history of influenza vaccination. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100041705, ChiCTR2100041706.

The World Health Organization noted that COVID-19 vaccination programmes could be leveraged to deliver influenza vaccination. In 2008, the International Federation of Pharmaceutical Manufacturers and Associations' (IFPMA) Influenza Vaccine Supply International Task Force (IVS) developed a survey method using the number of influenza vaccine doses distributed globally to estimate vaccination coverage rates. Seven hundred and ninety-seven million doses were distributed in 2021, representing a 205% increase over the 262 million doses distributed in 2004, exceeding the number of doses distributed during and after the 2009-2010 influenza pandemic. The most obvious explanation for the global increase is the enabling of critical elements of the vaccine ecosystem by decision-makers during the COVID-19 pandemic to reinforce implementation of influenza vaccination programs. Most of the improvements in performance of influenza programs during the COVID-19 pandemic can be classified in four categories: 1) promoting vaccination using tailored approaches for specific populations; 2) improving convenient access to influenza vaccines in COVID-safe settings; 3) improving reimbursement of seasonal influenza vaccination for priority groups; 4) maintaining the timing of vaccination to the autumn. In spite of the increase in rates of seasonal influenza vaccines distributed during the COVID-19 pandemic, globally, the rate of influenza dose distribution is sub-optimal, and a considerable proportion of the influenza infections remains preventable. To sustain the benefits from increased uptake of influenza vaccines, governments need to sustain the efforts made during the COVID-19 pandemic, and a number of global policy endeavours should be undertaken, including developing a clear global roadmap for achieving influenza control objectives, adopted by a WHA resolution, in line with the strategic objective 3 of the Global Influenza Strategy 2030, embedded in the Immunization Agenda 2030 (IA2030).

BACKGROUND: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females. METHODS: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500). FINDINGS: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses. INTERPRETATION: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases.

We report here the development and validation of CE-SDS method for purity analysis of Acellular Pertussis vaccine components viz. purified Pertussis toxin (PTx), purified Filamentous haemagglutinin (FHA), and Pertactinantigen (PRN). The method was found to be specific and showed excellent linearity at a concentration range of 15.62 µg/mL-1000 µg/mL for purified PTx, 31.25 µg/mL-1000 µg/mL for purified FHA, and 3.9 µg/mL-1000 µg/mL for PRN antigen. Method reported limit of quantification (LOQ) 31.25 µg/mL, 62.5 µg/mL, and 7.8 µg/mL for purified PTx, FHA, and PRN respectively. Method precision (repeatability and intermediate precision) for purity and molecular weight determination in product matrix was below 10% for all three proteins. Method comparability studies were performed with SDS-PAGE. CE-SDS demonstrated corroborating results with SDS-PAGE for the estimation of purity and molecular weight analysis. However, CE-SDS method exhibited better resolution capabilities for resolving all the sub-unit peaks of PTx and isoforms of purified FHA. CE-SDS method also demonstrated stability indicating potential and thus fits its intended purpose as an effective analytical tool for quality control of acellular pertussis-based vaccines.

Zika virus infection continues to be a global concern for human health due to the high-risk association of the disease with neurological disorders and microcephaly in newborn. Nowadays, no vaccine or specific antiviral treatment is available, and the development of safe and effective vaccines is yet a challenge. In this study, we obtained a novel subunit vaccine that combines two regions of zika genome, domain III of the envelope and the capsid, in a chimeric protein in E. coli bacteria. The recombinant protein was characterized with polyclonal anti-ZIKV and anti-DENV antibodies that corroborate the specificity of the molecule. In addition, the PBMC from zika-immune donors stimulated with the ZEC recombinant antigen showed the capacity to recall the memory T cell response previously generated by the natural infection. The chimeric protein ZEC was able to self-assemble after combination with an immunomodulatory specific oligonucleotide to form aggregates. The inoculation of BALB/c mice with ZEC aggregated and not aggregated form of the protein showed a similar humoral immune response, although the aggregated variant induced more cell-mediated immunity evaluated by in vitro IFNγ secretion. In this study, we propose a novel vaccine candidate against the zika disease based on a recombinant protein that can stimulate both arms of the immune system.

Marek's disease (MD) is a highly contagious viral neoplastic disease of chickens caused by Marek's disease virus (MDV), resulting in significant economic losses to the poultry industry worldwide. The commonly used live and/or vectored MDV vaccines are expensive to produce and difficult to handle due to the requirement of liquid nitrogen for manufacturing and delivering frozen infected cells that are viable. In this study, we aimed to develop a Newcastle disease virus (NDV) vectored MDV vaccine that can be lyophilized, stored, and transported at 4 °C. Four NDV LaSota (LS) vaccine strain-based recombinant viruses expressing MDV glycoproteins gB, gC, gE, or gI were generated using reverse genetics technology. The biological assessments showed that these recombinant viruses were slightly attenuated in vivo yet retained similar growth kinetics and virus titers in vitro compared to the parental LaSota virus. Vaccination of leghorn chickens (Lines 15I5x71 F1 cross) with these recombinant viruses via intranasal and intraocular routes conferred different levels of protection against virulent MDV challenge. The recombinant expressing the MDV gB protein, rLS/MDV-gB, protected vaccinated birds significantly against MDV-induced tumor formation when challenged at 14 days post-vaccination (DPV) but moderately at 5 DPV. Whereas the other three recombinants provided little protection against the MDV challenge. All four recombinants conferred complete protection against the velogenic NDV challenge. These results demonstrated that the rLS/MDV-gB virus is a safe and efficacious dual vaccine candidate that can be lyophilized and potentially mass-administered via aerosol or drinking water to large chicken populations at a meager cost.

INTRODUCTION: New extended half-life antibodies for the single-dose prevention of medically attended (MA) respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) have been developed for administration to all infants before or during their first RSV season. For infants born during the season, administration as soon as feasible after birth would provide optimal protection and minimize access disparities. The objective of this study was to assess the time from birth hospitalization discharge to the first outpatient visit (FOV) among US infants in order to determine optimal site of administration for the extended half-life antibody. MATERIAL AND METHODS: This retrospective, observational, time-to-event analysis uses the Merative™ MarketScan® Commercial and Multi-State Medicaid Databases. Time to FOV is reported separately for the COVID-19 and recent pre-COVID-19 eras and for commercially insured and Medicaid infants. RESULTS: Overall, 73.8 % of Medicaid infants had an FOV within 5 days as compared to 84.7 % of commercially insured infants. Estimates were higher during the COVID-19 era. Urban commercially insured infants had much higher FOV completion than their counterparts. Among Medicaid infants, urban Black and rural White infants were least likely to complete their FOV within 5 days of birth hospitalization discharge. DISCUSSION AND CONCLUSION: FOV within 5 days after birth hospitalization discharge for Medicaid infants is substantially lower than that of commercially insured infants. Approximately 1 in 4 Medicaid infants and 1 in 8 infants with commercial insurance did not have an outpatient visit within 5 days of birth hospitalization discharge. For US infants born during the RSV season, administration of extended half-life RSV antibodies in the newborn nursery prior to discharge would ensure optimal uptake and minimize access disparities.

BACKGROUND: Data on humoral and cellular immune responses against SARS-CoV-2 after receiving heterologous CoronaVac/ChAdOx-1 (CoVac/ChAd) vaccination in subjects with chronic obstructive pulmonary disease (COPD) are still limited. Therefore, we determined the neutralizing antibody (NAb) and T-cell responses against SARS-CoV-2 wild type (WT) and variants of concern (VOCs) in COPD patients. METHODS: The levels of NAb as well as specific CD4 and CD8 T-cell responses against SARS-CoV-2 WT and VOCs were determined in COPD patients before and after vaccination. RESULTS: Four weeks after vaccinations, the median levels of % inhibition of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants were significantly higher compared to pre-vaccination. The induction of NAb against Omicron was very low compared to other variants. At four weeks after vaccination, in comparison to pre-vaccination, the increasing trend of TNF-α-, IFN-γ-, IL-4-, IL-17-, IL-10-, and FasL-producing CD4 T-cells upon stimulation with WT spike peptides were demonstrated. No difference in T-cell responses to spike peptides of Alpha, Beta, and Delta variants and their WT homologs was observed. CONCLUSION: Heterologous CoVac/ChAd vaccine induced the production of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants, but low for Omicron in COPD patients. Induction of CD4 T-cell subset responses was slightly observed by this vaccine regimen. CLINICAL TRIALS REGISTRY: This study was approved by the Clinical Trials Registry (Study ID: TCTR20210822002).

OBJECTIVE: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children. METHODS: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-μg) or half-dose (5-μg) BNT162b2 vaccines as follows: CoronaVac/10-μg-BNT162b2 (Group 1), CoronaVac/5-μg-BNT162b2 (Group 2), 10-μg-BNT162b2/10-μg-BNT162b2 (Group 3), or 10-μg-BNT162b2/5-μg-BNT162b2 (Group 4). A subset of participants from each arm received 10-μg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported. RESULTS: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter. CONCLUSION: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.

BACKGROUND: The routine immunization program for children is a primary strategy and a core part of vaccination. Achieving and maintaining high level of vaccination coverage are important to reduce morbidity and mortality caused by vaccine-preventable diseases. In Beijing, annual coverage surveys have been conducted since 2005. It is necessary and possible to assess the level and trend of routine vaccination coverage of children in Beijing as well as the disruption of coronavirus disease 2019 (COVID-19) pandemic and provide the reference for the further improve the vaccination coverage. METHODS: The data of 61,521 children aged 1-3 years in the vaccination coverage surveys during 2005-2021 were analyzed by Beijing Center for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the data and the difference of vaccination coverage within the time period. RESULTS: More than 99 % of participants had immunization cards and electronic immunization records. The concordance rate of both records were also over 99 %. During 2011-2019, the rates of on-time and in-time vaccination of each routine vaccine reached 96 % or more and increased significantly (all P values <0.05), compared with that of 2005-2010. All rates of the investigated vaccine, except for Bacillus Calmette-Guérin vaccine (BCG) and the first dose of hepatitis B vaccine (HepB), decreased in 2020-2021 significantly (all P values <0.05). For the causes of failing to vaccinate on time, delayed vaccination accounted for 47.82 %. The top two vaccines to be missed were the first dose of hepatitis A vaccine and the 4th dose of diphtheria-tetanus-acellular pertussis vaccine, accounting for 21.41 % and 20.79 %, respectively. The main reason for zero-dose/drop-out vaccination was "Guardians regarded the immunization service time as inappropriate", accounting for 72.27 %. CONCLUSION: The coverage level and service quality of routine immunization in Beijing were relatively high. However, as influenced by COVID-19 epidemics, both on-time and in-time vaccination rates decreased significantly, except for BCG and HepB. Under the background of COVID-19 pandemic, the keys to maintain high level of vaccination coverage include flexible immunization service time to ensure the guardians bringing their children for vaccination timely, and more attention from providers to the doses after children's first birthday.

Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Prophylactic HPV vaccines have shown benefits in preventing subsequent HPV-related disease when administered before or soon after treatment. Based on our understanding of the HPV life cycle and vaccine mechanism of action, prophylactic HPV vaccination is not expected to clear active persistent HPV infection or unresected HPV-associated dysplastic tissue remaining after surgery. However, vaccination may reasonably be expected to prevent new HPV infections caused by a different HPV type as well as re-infection with the same HPV type, whether from a new exposure to an infected partner or through autoinoculation from an adjacent or distant productively infected site. In this review, we describe the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment and discuss potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines. We also consider how precise terminology relating to the use of prophylactic vaccines in this population is critical to avoid the incorrect implication that prophylactic vaccines have direct therapeutic potential, which would be counter to the vaccine's mechanism of action, as well as considered off-label. In other words, the observed effects occur through the known mechanism of action of prophylactic HPV vaccines, namely by preventing virus of the same or a different HPV type from infecting the patient after the procedure.

BACKGROUND: Although COVID-19 booster vaccination is widely recommended, there is limited long-term, population-level, real-world evidence on the magnitude of improved protection against severe COVID-19 conferred by boosting with monovalent COVID-19 vaccines developed against ancestral SARS-CoV-2, especially in low- or middle-income countries. We present interim results from the first large-scale assessment of the relative vaccine effectiveness (rVE) of first and second booster doses against severe COVID-19 in a low-/middle-income country. METHODS: REFORCO-Brazil is an ongoing, test-negative case-control study (NCT05697705) utilizing Brazil national severe acute respiratory syndrome (SARS) surveillance and vaccination data. In SARS hospitalizations from August 1, 2021 to July 31, 2022, we matched test-positive (via SARS-CoV-2 antigen/reverse transcription polymerase chain reaction [RT-PCR]) cases and test-negative case-controls (via RT-PCR) based on admission date, preceding vaccinations, and age. We evaluated the rVEs of four monovalent COVID-19 vaccines (AZD1222, Ad26.COV2.S, CoronaVac, and BNT162b2) as second boosters compared with any first boosters received ≥4 months previously, and as first boosters compared with primary-series vaccinations completed ≥4 months previously. RESULTS: The overall rVE of second boosters, from 5668 (2238 test-positive) evaluated hospitalizations, was 24.7 % (95 % confidence interval [CI]: 12.6-35.1); the overall rVE of first boosters, from 30,272 (12,063 test-positive) hospitalizations, was 46.8 % (95 % CI: 43.3-50.0). The rVEs of AZD1222 and BNT162b2 were similar: 29.4 % (95 % CI: 8.6-45.5) and 25.5 % (95 % CI: 4.2-42.2), respectively, for second boosters; and 42.5 % (95 % CI: 28.0-54.0) and 50.8 % (95 % CI: 47.5-54.0), respectively, for first boosters. In general, rVEs were higher in elderly (≥80 years) and immunocompromised/high-risk individuals. CONCLUSIONS: Our results support the use of AZD1222 and other adenoviral/mRNA vaccine boosters to maintain protection against COVID-19 hospitalization from Omicron subvariants, including in elderly and immunocompromised individuals at increased risk of accelerated waning or severe outcomes.

Porcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms.

SARS-CoV-2 resulted in the COVID-19 pandemic which, to date, has resulted in an estimated loss of over 15 million human lives globally and continues to have negative social, and economic implications worldwide. Vaccine platforms that can be quickly updated to counter newly emerging SARS-CoV-2 variants are critical in combating the COVID-19 pandemic. Messenger RNA-based SARS-CoV-2 vaccines can be easily updated and have shown superior efficacy over other vaccine types, yet their high cost, reactogenicity, and stringent need for ultracold storage limit their accessibility. Global access to economic, safe, and effective SARS-CoV-2 vaccines is a critical step toward reducing COVID-19-associated mortality and ending the pandemic. Several protein-based SARS-CoV-2 vaccines targeting the spike protein (or its receptor-binding domain) have demonstrated safety and efficacy in clinical studies. Moreover, protein-based vaccines can be updated to immunize against new virus variants. Protein-based vaccines do not contain live viruses and are safe to use in immunocompromised and elderly populations, and can be optimized to improve the immune outcome in these poorly immunoresponsive individuals by using adjuvants. SARS-CoV-2 shows high genetic variability, similar to other RNA viruses, and protein-based vaccines are an economically feasible vaccine platform that can be used to design new vaccines with durable protective immunity, in addition to expanding the vaccine coverage.

Oral cholera vaccine is one of the key interventions used in our fight to end the longest pandemic of our time, cholera. The immune response conferred by the currently available cholera vaccines, as measured by serum antibody levels, is variable amongst its recipients. We undertook a genome wide association study (GWAS) on antibody response to the cholera vaccine; globally, the first GWAS on cholera vaccine response. We identified three clusters of bi-allelic SNPs, in high within-cluster linkage disequilibrium that were moderately (p < 5 × 10-6) associated with antibody response to the cholera vaccine and mapped to chromosomal regions 4p14, 4p16.1 and 6q23.3. Intronic SNPs of TBC1D1 comprised the cluster on 4p14, intronic SNPs of TBC1D14 comprised that on 4p16.1 and SNPs upstream of TNFAIP3 formed the cluster on 6q23.3. SNPs within and around these clusters have been implicated in immune cell function and immunological aspects of autoimmune or infectious diseases (e.g., diseases caused by Helicobacter pylori and malarial parasite). 6q23.3 is a prominent region harbouring many loci associated with immune related diseases, including multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus, as well as IL2 and INFα response to a smallpox vaccine. The gene clusters identified in this study play roles in vesicle-mediated pathway, autophagy and NF-κB signaling. No significant effect of O blood group on antibody response to the cholera vaccine was observed in this study.

The European Society of Pediatric Infectious Diseases (ESPID) hosted the third Group B Streptococcus (GBS) Research Session in Athens on 11th May 2022, providing researchers and clinicians from around the world an opportunity to share and discuss recent advances in GBS pathophysiology, molecular and genetic epidemiology and how these new insights can help in improving prevention and control of early- and late-onset GBS disease. The meeting provided a state-of-the-art overview of the existing GBS prevention strategies and their limitations, and an opportunity to share the latest research findings. The first presentation provided an overview of current GBS prevention and treatment strategies. In the second presentation, the genomic and antimicrobial resistance profiles of invasive and colonizing GBS strains were presented. The third presentation explained the association of intrapartum antibiotic prophylaxis (IAP) with the development of late-onset disease (LOD) and the interplay of host innate immunity and GBS. The fourth presentation evaluated the role of genomics in understanding horizontal GBS transmission. The fifth presentation focused on the zoonotic links for certain GBS lineages and the last presentation described the protective role of breastmilk. Talks were followed with interactive discussions and concluded with recommendations on what is needed to further GBS clinical research; these included: (i) the development of better risk stratification methods by combining GBS virulence factors, serological biomarkers and clinical risk factors; (ii) further studies on the interplay of perinatal antimicrobials, disturbances in the development of host immunity and late-onset GBS disease; (iii) routine submission of GBS isolates to reference laboratories to help in detecting potential clusters by using genomic sequencing; (iv) collaboration in animal and human GBS studies to detect and prevent the emergence of new pathogenic sequence types; and (v) harnessing the plethora of immune factors in the breastmilk to develop adjunct therapies.

BACKGROUND: Hepatitis A is an inflammation of the liver caused by the hepatitis A virus (HAV). It is transmitted mainly because of poor personal hygiene via the faecal/oral route through ingestion of contaminated food or water or through the direct contact with an infectious person. Though most of the infected individuals recover from the infection, a few may develop fatal fulminant hepatitis. In this randomized, multicenter study, immunogenicity and safety of Havisure™ vaccine of Human Biologicals Institute was compared with Havrix® vaccine. METHODS: The study was carried out in 528 eligible healthy subjects, in two age groups across eight centres in India. Group A included subjects of 19-49 years and Group B subjects of 12 months to below 19 years of age. All subjects received two doses of either Havisure™ vaccine or Havrix® vaccine as per randomization at six months interval. Blood samples for antibody titre estimation were collected before vaccination and 4-6 weeks after 2nd dose of vaccination. Immunogenicity was assessed by estimating seroconversion rate, seroprotection rate, and geometric mean titres of antibodies. Safety was evaluated by collection and analysis of data on solicited and unsolicited adverse events. RESULTS: Of 528 enrolled subjects, 493 subjects completed the study. There was 100% seroconversion and seroprotection in both the vaccine arms. There was no statistical difference in the geometric mean titres between the two vaccine arms. Pain and swelling at the site of injection were the most common local adverse events whereas fever and headache were the most common systemic adverse events observed in both vaccine arms. No serious adverse event was reported in the study. CONCLUSION: The study results indicate that the Havisure™ vaccine is immunogenic and safe when administered to healthy subjects of 12 months to 49 years of age, and is non-inferior to Havrix® Vaccine.

We assessed COVID-19 vaccination (≥1 dose) status as influenced by sociodemographic factors (i.e., age, gender, race/ethnicity, education, income, and parent or guardian status), healthcare provider recommendation, and personal vaccine hesitancy among Arkansas residents in October 2022. We asked: did the likelihood of vaccination differ across sociodemographic groups of Arkansas during this period of the pandemic? Is COVID-19 vaccination associated with recommendations from healthcare providers and/or COVID-19 vaccine hesitancy? We analyzed data from a random sample survey of adults in Arkansas (N = 2,201). Three in four adults self-reported vaccination against COVID-19 in October 2022. We found both positive and negative association between COVID-19 vaccination and age, gender, race/ethnicity, education, income, healthcare provider recommendation, and vaccine hesitancy. We highlight racial differences in COVID-19 coverage and the higher odds of COVID-19 vaccination among Black adults compared to White adults in particular, which has broad implications for the study of vaccine coverage and hesitancy. We also discuss implications of our findings regarding healthcare provider recommendations to be vaccinated against COVID-19.

OBJECTIVE: The present study aims to estimate the frequency of COVID 19 infections in vaccinated health personnel at a Los CObos Medical Center in Bogotá, Colombia. The percentage of people positive to the PCR test and their clinical characteristics were analyzed. METHODS: We performed a cross-sectional study. The primary study variable was the COVID vaccination registry. We analyzed sex, age, signs, and symptoms. Multivariable logistic regression was applied to assess changes over time and to identify variables associated with vaccination in target groups. RESULTS: A cohort of 999 people working at Los Cobos Medical Center and followed from March to August 2021. The average age of this cohort was 37.0 years (devest = 10.5 years), 67.7 % were women. Two hundred eleven physicians, 287 nurses, 305 assistants, and 196 clerks follows. In addition, 8.4 % to be PCR positive after vaccination. The average age was 36.0 (devest = 23.4 years), 59 women and 25 men. Of these, 15 were administrative, 14 were doctors, 29 nurses, and 26 nursing assistants. The vaccination status found that 21.4 % do not vaccinates, 7.1 % were partially vaccinated, and 71.4 % with a complete schedule. When questioned about symptoms in these patients, 4.0 % were symptomatic, and 5.9 % were asymptomatic. CONCLUSIONS: A recent epidemiological study involving 12,364 health workers with a mean age of 38 years quantifies the protection in six months from the vaccine. The presence of antibodies was associated with 83 % protection against active SARS-CoV-2 infection (PCR positivity during the study period), which confirms the existence of protective Immunity at levels comparable to those obtained by the approved vaccines; our study found effectiveness of 92.6 %. Higher than that found in this study, possibly explained by the characteristics of the individuals included.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

BACKGROUND: The national immunization program in Mexico includes a 3-dose primary series of pertussis vaccine and a toddler booster dose. In Mexico, whole-cell pertussis vaccines (wP) were switched in 2007 to acellular pertussis vaccines (aP). METHODS: This retrospective study using Mexican National Databases of Health and population surveillance (2000-2019) assessed the incidence of pertussis, infant pertussis vaccination coverage, and vaccine effectiveness (VE) against clinically-diagnosed and/or laboratory-confirmed pertussis in children aged 6.5-18.5 or 24.5 months for the primary series, and children aged 18.5 or 24.5-48.5 months for the toddler booster. RESULTS: The incidence of pertussis sharply increased in 2012 and was highest in 2012, 2015, and 2016 (0.84-0.94/100,000 person-years). Coverage was highest for the first dose in the primary series, decreasing for each subsequent dose. The VE against notified pertussis was 96.4% (95% CI: 94.7, 97.6) for the first three doses of wP vaccine (2000-2007) and 95.7% (95% CI: 95.1, 96.2) for the first three doses of aP vaccine (2008-2019). CONCLUSIONS: Our findings suggested high levels of vaccine effectiveness overall were achieved for the aP and wP vaccines in Mexico between 2000 and 2019.