BACKGROUND: High pneumococcal carriage density has been associated with severe pneumonia in some settings. The impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal carriage density has been variable. The aim of this systematic literature review is to describe the effect of PCV7, PCV10 and PCV13 on pneumococcal colonisation density in children under five years old. METHODS: We included peer reviewed English literature published between 2000 and 2021 to identify relevant articles using Embase, Medline and PubMed. Original research articles of any study design in countries where PCV has been introduced/studied were included. Quality (risk) assessment was performed using tools developed by the National Heart Brain and Lung Institute for inclusion in this review. We used a narrative synthesis to present results. RESULTS: Ten studies were included from 1941 articles reviewed. There were two randomised controlled trials, two cluster randomised trials, one case control study, one retrospective cohort study and four cross sectional studies. Three studies used semiquantitative culture methods to determine density while the remaining studies used quantitative molecular techniques. Three studies reported an increase in density and three studies found a decrease in density among vaccinated compared with unvaccinated children. Four studies found no effect. There was considerable heterogeneity in the study populations, study design and laboratory methods. CONCLUSION: There was no consensus regarding the impact of PCV on pneumococcal nasopharyngeal density. We recommend the use of standardised methods to evaluate PCV impact on density.

A recombinant protective antigen anthrax vaccine (GC1109) is being developed as a new-generation vaccine by the Korea Disease Control and Prevention Agency. In accordance with the ongoing step 2 of phase II clinical trials, the immunogenicity and protective efficacy of the booster dose of GC1109 were evaluated in A/J mice after 3 serial vaccinations at 4-week intervals. The results indicated that the booster dose significantly increased the production of anti-protective antigen (PA) IgG and toxin-neutralizing antibody (TNA) compared with those of the group without booster. An enhanced protective effect of the booster dose was not observed because the TNA titers of the group without booster were high enough to confer protection against spore challenge. Additionally, the correlation between TNA titers and probability of survival was determined for calculating the threshold TNA titer levels associated with protection. The threshold 50 % neutralization factor (NF50) of TNA showing 70 % probability of protection was 0.21 in A/J mice with 1,200 LD50 Sterne spores challenge. These results indicate that GC1109 is a promising candidate as a new-generation anthrax vaccine and that a booster dose might provide enhanced protection by producing toxin-neutralizing antibodies.

OBJECTIVE: The objectives of this study were to evaluate parental confidence and attitudes towards immunization in urban Guatemala between private versus public health systems and their impact on vaccination timeliness in their children. METHODS: A cross-sectional survey was conducted in parents 6-18-month-old children who attended well-child outpatient clinics from two health systems (public employee-based insurance and private health care) in Guatemala City from November 2017 through August 2018. Parental demographics, household characteristics, food insecurity, vaccine hesitancy using the WHO SAGE Vaccine Hesitancy Scale, and information on parental use of social media platforms and vaccine information sources were collected. RESULTS: Five hundred-three parents were surveyed, most of them mothers. Only 9 parents reported they had previously refused a vaccine for their child: 8 (3.2 %) from private clinics and 1 (0.4 %) from the public clinic (p = 0.02). Significantly more children attending private clinics (226, 90.4 %) were shown to have a delay in any of their vaccines scheduled for the first 2 years of life compared to those in the public clinic (169, 66.8 %; p < 0.01). Children of parents having a college degree (84.5 vs 70.1 %; p < 0.001), earning more than US$ 1,000 per month (81.5 vs 70.7 %; p < 0.001), and having a computer at home (81.4 vs 70.2; p = 0.007) were more likely to have any delays in the scheduled vaccines. Parents seeking care at private clinics were 1.14 times more at risk of delaying a vaccine compared to those at the public clinic, adjusted for other covariates (p = 0.03, 95 % CI: 1.01, 1.28). CONCLUSIONS: In Guatemala, children receiving immunizations at private clinics were significantly more likely than those attending public clinics to be delayed in their immunization schedule and to remain more days without the recommended protection, especially for third doses of the primary vaccine series.

A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection.

Flaviviruses are antigenically related. We evaluated the immunogenicity and efficacy of Takeda's purified inactivated Zika vaccine (PIZV) candidate in macaques previously vaccinated with several commercially available heterologous flavivirus vaccines. Heterologous flavivirus vaccination did not elicit Zika virus (ZIKV) neutralizing antibodies and did not impact neutralizing antibody titers after one dose of PIZV. After a second PIZV dose previous vaccination with flavivirus vaccines had variable impact on ZIKV neutralizing antibody titers. However, all macaques were protected against viremia after Zika virus challenge 8-12 months post-PIZV vaccination. Therefore, vaccine-induced immunity against heterologous flavivirus vaccines does not impact PIZV efficacy in macaques.

BACKGROUND: SARS-CoV-2 vaccination of all age-eligible populations is an important part of the COVID-19 pandemic response. In Ontario, vaccination coverage in 5-to-11-year-old children has remained lower than in other age groups. We sought to understand pediatricians' perception, practices, and barriers to SARS-CoV-2 vaccination in children, particularly children aged 5-to-11 years, to inform interventions and promote capacity of pediatricians as vaccinators and vaccination promoters. METHODS: This is a descriptive, cross-sectional study consisting of an online self-administered questionnaire distributed to 1,313 pediatricians in Ontario. Descriptive statistics, including Chi-square or Fisher's exact tests, were performed. RESULTS: In total, 152 Pediatricians responded (11.6% response rate), from February 17, 2022 to March 17, 2022. 78% of respondents were general pediatricians and 22% were pediatric subspecialists. Median years of practice was 17 (8-31), with 68% female, 32% male. Most pediatricians thought it was unlikely that children aged 5-to-11 years would become seriously ill from acute COVID-19 caused by Delta (66%) or Omicron (80%). 92% were very likely to recommend the COVID-19 vaccine for children aged 5-to-11 years. COVID-19 vaccine was perceived as safe, with higher safety perception in children aged 5-to-11 compared to 12-to-17 years (p < 0.0001). COVID-19 vaccines were thought to be effective in reducing hospitalization or severe illness, and reducing SARS-CoV-2 infection, with higher perceived effectiveness against Delta compared to Omicron (p < 0.0001). 97% felt confident counselling caregivers of children aged 5-to-11 years on the COVID-19 vaccine. Few pediatricians did not feel confident in accessing resources for health professionals (6%) or for patients/caregivers (12%). CONCLUSIONS: Most surveyed pediatricians were very likely to recommend COVID-19 vaccination for children aged 5-to-11-years, perceived COVID-19 vaccines as safe and effective, and felt confident in their COVID-19 vaccine counselling for children aged 5-to-11 years. However, there remains areas for further training and capacity development.

BACKGROUND: The immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness. METHODS: We used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases). RESULTS: We identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43-0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53-1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65-69 and 80-years, 5 months in 70-79 years. CONCLUSIONS: Our study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously.

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) show an immune dysfunction with increased risk of infections and poor response to vaccination. Streptococcus pneumoniae is a common cause of morbidity and mortality in CLL patients. In a previous randomized clinical trial, we found a superior immune response in CLL patients receiving conjugated pneumococcal vaccine compared to non-conjugated vaccine. The response to revaccination in CLL patients is scarcely studied. In this study, early humoral response to repeated revaccinations with pneumococcal vaccines was evaluated, by determination of B cell subsets and plasmablast dynamics in peripheral blood. METHOD: CLL patients (n = 14) and immunocompetent controls (n = 31) were revaccinated with a 13-valent pneumococcal conjugate vaccine (PCV13) after previous primary immunization (3-6 years ago) with PCV13 or a 23-valent pneumococcal polysaccharide vaccine (PPSV23). Eight weeks after the first revaccination, all CLL patients received a second revaccination with PCV13 or PPSV23. B cell subsets including plasmablasts were analyzed in peripheral blood by flow cytometry, before and after the first and the second revaccination. RESULTS: None of the CLL patients, but all controls, had detectable plasmablasts at baseline (p < 0.001). After the first revaccination with PCV13, the plasmablast proportions did not increase in CLL patients (p = 0.13), while increases were seen in controls (p < 0.001). However, after a second revaccination with PCV13 or PPSV23, plasmablasts increased compared to baseline also in CLL patients (p < 0.01). If no response was evident after first revaccination, only a second revaccination with PCV13 increased plasmablasts in contrast to PPSV23 revaccination. Patients with hypogammaglobulinemia and ongoing/previous CLL specific treatment responded poorly, also to a second revaccination. CONCLUSION: In CLL patients, pneumococcal revaccination induced minor early plasmablast response compared to controls, but the response improved using a strategy of repeated doses with of conjugated T cell dependent pneumococcal vaccine.

BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced for childhood vaccination in Brazil's National Immunization Program in 2010. After nine years of PCV10 use, we investigated the carriage prevalence, capsular types, antimicrobial resistance and risk factors among children living in Niterói city, RJ, Brazil. METHODS: Between September and December 2019, we conducted a cross-sectional study and recruited children under 6 years of age. Antimicrobial susceptibility was evaluated by the disk-diffusion method and MICs to beta-lactams and macrolides were determined by E-test®. Capsular types were deduced by multiplex PCR. Logistic regression was used to predict risk factors for pneumococcal carriage. RESULTS: Seventy-five (17.4%) of the 430 children were pneumococcal carriers. The most frequent capsular types were 6C/D (14.7%), 11A/D (13.3%), and 23B (9.3%). PCV10 serotypes represented 5.3%. All isolates were susceptible to levofloxacin, linezolid, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) made up 37.3%, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 μg/ml and 0.064-4.0 μg/ml, respectively. Of the 19 (25.3%) erythromycin-resistant (ERY-R) isolates (macrolide MICs of 6 to >256 μg/ml), most had the cMLSB phenotype (84.2%) and carried the erm(B) gene (73.7%). We detected 17 (22.6%) multidrug-resistant (MDR) isolates, strongly associated with serotype 6C/D. Presence of any symptoms, chronic diseases, childcare center attendance, living with young siblings, slum residence, and unstable income were predictors of pneumococcal carriage. CONCLUSIONS: Long-term universal childhood use of PCV10 has nearly eliminated carriage with PCV10 serotypes, but the high frequency of MDR isolates, especially associated with serotype 6C/D, remains a concern. Replacing PCV10 with PCV13 should reduce the proportion of ERY-R isolates and PNSP by at least 14% and 18%, respectively.

INTRODUCTION: In 2016, Australia launched a whole life immunisation register, the Australian Immunisation Register (AIR), building on a universal childhood register established in 1997. Immunisation Information Systems are well established in Europe, the US and elsewhere. However, a national system covering immunisation across the lifespan, with complete capture of the population and satisfactory data quality, is rare. METHODS: A national workshop was convened in 2016 with key stakeholders from the government, new and existing vaccine users, and vaccine providers to review the ideal features of the AIR to ensure optimal effectiveness. This workshop focused on the functionality needed to identify population groups newly included in the register and support the achievement of high immunisation coverage in these groups eligible for National Immunisation Program vaccines. RESULTS: Key recommendations included the need for bidirectional data flow between the AIR and providers; systematic approaches to the capture and recording of accurate and complete data to ascertain important denominators for subpopulations, includingAboriginal and Torres Strait Islander status, medical risk factors, occupation, ethnicity, country of birth, and vaccines given during pregnancy; linkage with other government datasets including notifiable diseases; the capture of adverse events following immunisation; ease of access by patients, providers; and by researchers. CONCLUSIONS: Some recommendations from the workshop have informed the development and future utility of the AIR. Some recommendations from the workshop have been integrated into the current iteration of the AIR, which is more important than ever given the roll-out of COVID-19 vaccines. The accuracy and validity of data have subsequently improved through data entry controls, data integrity checks and reporting requirements. Access to AIR data for research remains protracted and costly, limitingresearch potential.

Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS.

In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21-33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this.

Bovine respiratory disease is the greatest threat to calf health. In this study, colostrum-fed dairy X beef calves were vaccinated at ∼30 days of age with an adjuvanted parenteral vaccine containing modified live bovine viral diarrhea virus (BVDV) type 1 and type 2, bovine herpesvirus 1 (BHV-1), bovine parainfluenza type 3 virus (PI3V) and bovine respiratory syncytial virus (BRSV) andM. haemolyticatoxoid (Group 1), or intranasal temperature-sensitive BHV-1, BRSV and PI3V concurrently witha parenteral vaccine containing modified live BVDV type 1 and type 2 andM. haemolyticatoxoid (Group 2) or a placebo (Group 3). The calves were challenged ∼150 days post vaccination intranasally with BVDV 1b and then 7 days later intratracheally withM. haemolytica. The calves wereeuthanized 6 days after theM. haemolyticachallenge. Clinical signs following BVDV infection were similar in all groups. There was increased rectal temperatures in the Groups 2 and 3 on day 3 and in Group 3 on days 8-13. Group 1 animals had a slight leukopenia following BVDV infection while Groups 2 and 3 had greater leukopenia. BVDV type 1 and 2 serum titers increased in Group 1 following vaccination while these titers waned in Groups 2 and 3. There were higher levels of BVDV in the buffy coats and nasal samples in Group 2 and Group 3 versus Group 1 (p < 0.01). Interferon-gamma response was higher (p < 0.01) in Group 1 animals than Groups 2 and 3. Group 1 had the lowest percent pneumonic tissue (1.6%) while Group 2 vaccinates had 3.7% and the control Group 3 was 5.3%. Vaccination in the face of maternal antibody with a parenteral adjuvanted vaccine resulted in better protection than the regimen of an intranasal vaccine anda parenteral adjuvanted BVDV andM haemolyticacombination vaccine in a BVDV-M. haemolyticadual challenge.

Swine influenza A virus (swIAV) is a major pathogen affecting pigs with a huge economic impact and potentially zoonotic. Epidemiological studies in endemically infected farms permitted to identify critical factors favoring on-farm persistence, among which maternally-derived antibodies (MDAs). Vaccination is commonly practiced in breeding herds and might be used for immunization of growing pigs at weaning. Althoughinterference between MDAs and vaccination was reported in young piglets, its impact on swIAV transmission was not yet quantified. To this aim, this study reports on a transmission experiment in piglets with or without MDAs, vaccinated with a single dose injection at four weeks of age, and challenged 17 days post-vaccination. To transpose small-scale experiments to real-life situation, estimated parameters were used in a simulation tool to assess their influence at the herd level. Based on a thorough follow-up of the infection chain during the experiment, the transmission of the swIAV challenge strain was highly dependent on the MDA status of the pigs when vaccinated. MDA-positive vaccinated animals showed a direct transmission rate 3.6-fold higher than the one obtained in vaccinated animals without MDAs, estimated to 1.2. Vaccination nevertheless reduced significantly the contribution of airborne transmission when compared with previous estimates obtained in unvaccinated animals. The integration of parameter estimates in a large-scale simulation model, representing a typical farrow-to-finish pig herd, evidenced an extended persistence of viral spread when vaccination of sows and single dose vaccination of piglets was hypothesized. When extinction was quasi-systematic at year 5 post-introduction in the absence of sow vaccination but with single dose early vaccination of piglets, the extinction probability fell down to 33% when batch-to-batch vaccination was implemented both in breeding herd and weaned piglets. These results shed light on a potential adverse effect of single dose vaccination in MDA-positive piglets, which might lead to longer persistence of the SwIAV at the herd level.

BACKGROUND: Vaccination is a key public health intervention that can reduce excess mortality in humanitarian contexts. Vaccine hesitancy is thought to be a significant problem requiring demand side interventions. Participatory Learning and Action (PLA) approaches have proven effective in reducing perinatal mortality in low income settings and we aimed to apply an adapted approach in Somalia. METHODS: A randomised cluster trial was implemented in camps for internally displaced people near Mogadishu, from June to October 2021. An adapted PLA approach (hPLA) was used in partnership with indigenous 'Abaay-Abaay' women's social groups. Trained facilitators ran 6 meeting cycles that addressed topics of child health and vaccination, analysed challenges, and planned and implemented potential solutions. Solutions included a stakeholder exchange meeting involving Abaay-Abaay group members and services providers from humanitarian organisations. Data was collected at baseline and after completion of the 3 month intervention cycle. RESULTS: Overall, 64.6% of mothers were group members at baseline and this increased in both arms during the intervention (p = 0.016). Maternal preference for getting young children vaccinated was >95% at baseline and did not change. The hPLA intervention improved the adjusted maternal/caregiver knowledge score by 7.9 points (maximum possible score 21) compared to the control (95% CI 6.93, 8.85; p < 0.0001). Coverage of both measles vaccination (MCV1) (aOR 2.43 95% CI 1.96, 3.01; p < 0.001) and completion of the pentavalent vaccination series (aOR 2.45 95% CI 1.27, 4.74; p = 0.008) also improved. However, adherence to timely vaccination did not (aOR 1.12 95% CI 0.39, 3.26; p = 0.828). Possession of a home-based, child health record card increased in the intervention arm from 18 to 35% (aOR 2.86 95% CI 1.35, 6.06; p = 0.006). CONCLUSION: A hPLA approach, run in partnership with indigenous social groups, can achieve important changes in public health knowledge and practice in a humanitarian context. Further work to scale up the approach and address other vaccines and population groups is warranted.

INTRODUCTION: This study aimed to assess the effect of a reduced dose regime (1 + 1) of PCV10 and PCV13 along with 3-dose regimes on pneumococcal vaccine-type (VT) carriage and immunogenicity in the first two years of life in PCV-naïve Indian children. METHODS: A total of 805 healthy infants aged 6-8 weeks were randomised to 7 groups (n = 115). Six groups received SynflorixTM(PCV10) or Prevenar13TM(PCV13) in the following schedules: 3 + 0 (three primary at 6, 10, and 14 weeks); 2 + 1 (two primary 6 and 14 weeks with booster at 9 months; 1 + 1 (one primary at 14 weeks with booster at 9 months). The 7th group was a PCV-naïve control group. Nasopharyngeal swabs were collected at 6, 18 weeks, 9, 10, 15, and 18 months of age. Venous blood samples were collected at 18 weeks, 9, 10, and 18 months of age for assessment of sero-specific IgG antibodies. Additionally, functional activity using a serotype specific opsonophagocytic assay (OPA) was assessed at 10 and 18 months of age in a subset (20%) of participants. RESULTS: All schedules of PCV13 showed significant 13VT carriage reduction in the second year of life as compared to control. At 15 months of age, PCV13 (1 + 1) showed 45 % reduction in 13VT-carriage compared to the control [OR = 0.55 (95% CI; 0.31-0.97), p= 0.038]. None of the PCV10 schedules showed significant reduction in 10VT carriage in the second year. Although not powered for these outcomes, at 18 months of age, 1 + 1 and 2 + 1 schedules of both vaccines demonstrated higher sero-responders for all serotypes, higher geometric mean concentrations (GMC) for all serotypes except 23F [with both vaccines], higher percent OPA responders and OPA geometric mean titres (GMT) compared to the 3 + 0 schedules for all serotypes. CONCLUSION: The reduced dose schedule (1 + 1) of PCV13 results in significant VT-carriage reduction in the second year of life. Immune protection provided by 1 + 1 schedules of PCV10 and PCV13 in the second year of life is comparable to WHO-recommended 3-dose schedules.

Delays in vaccinating communities of color to COVID-19 have signaled a need to investigate structural barriers to vaccine uptake, with mass incarceration demanding greater characterization as a potential factor. In a nationally representative survey from February-March 2021 (N = 1,157), exposure to the criminal legal system, defined as having been incarcerated in prison or jail or having had a family member or close friend incarcerated, was associated with higher odds for COVID-19 vaccine deliberation. Individuals with criminal legal system exposure reported lower confidence in physician recommendation as a reason to get vaccinated. They were also more likely to decline vaccination out of fear it would cause COVID-19 infection, and that the vaccine might be promoted as a political tool. Our analysis suggests that populations impacted by the criminal legal system would benefit from targeted vaccine outreach by trusted community members who can address distrust during current and future pandemics.

Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed.

The increasing awareness of endotoxin contamination has raised important questions during the study of the mechanism of action of the vaccine adjuvants. The endotoxins or lipopolysaccharides (LPS) can contaminate vaccine formulations contributing to result misinterpretations of the in vitro and in vivo studies. In this short communication, we considered the suitability of the Limulus amebocyte lysate (LAL) assay to quantify chitosan (Chit) nanoparticle (NP) endotoxin contamination to use them in a comparative in vitro immunotoxicology study using both LPS-free (LF) and non-LF Chit NPs. It was shown that chit NPs had a masking effect on endotoxin levels, hampering a reliable conclusion about the effect of their contamination. Neither non-LF nor LF Chit NPs induced the production of ROS in RAW 264.7 cells or IL-6 and TNF-α in PBMCs. The lack of effect of non-LF NPs was not expected and likely due to the NPs masking effect, more evident for higher deacetylation degree Chit. Overall, to prevent questionable results, nanomaterials should be produced under endotoxin-free conditions.

OBJECTIVES: The first 3-antigen hepatitis B vaccine was approved by the United States (US) Food and Drug Administration in November 2021 and was recommended by the Centers for Disease Control and Prevention in 2022. We estimated the cost-effectiveness of this 3-antigen vaccine (PreHevbrio™) relative to the single-antigen vaccine, Engerix-BTM, to prevent hepatitis B virus (HBV) infection among US adults. METHODS: A cost-effectiveness model was developed using a combined decision-tree and Markov structure to follow 100,000 adults over their remaining lifetimes after vaccination with either the 3-antigen or single-antigen vaccine. Outcomes from societal and healthcare sector perspectives were calculated for adults aged 18-44, 45-64, and ≥65 years; adults with diabetes; and adults with obesity. Seroprotection rates were obtained from the phase3, head-to-head PROTECT trial (NCT03393754). Incidence, vaccine costs, vaccine adherence rates, direct and indirect costs, utilities, transition probabilities, and mortality were obtained from published sources. Health outcomes and costs (2020USD) were discounted 3% annually and reported by vaccine and population. One-way sensitivity and scenario analyses were conducted. RESULTS: In the model, the 3-antigen vaccine led to fewer HBV infections, complications, and deaths compared with the single-antigen vaccine in all modeled populations due to higher rates and faster onset of seroprotection. Compared with the single-antigen vaccine, the 3-antigen vaccine had better health outcomes, more quality-adjusted life-years (QALYs), and lower costs in adults aged 18-64 years, adults with diabetes, and adults with obesity (dominant strategy). For adults aged ≥65 years, the 3-antigen vaccine was cost-effective compared with the single-antigen vaccine ($26,237/QALY gained) below common willingness-to-pay thresholds ($50,000-$100,000/QALY gained). In sensitivity analyses, results were sensitive to vaccine cost per dose, incidence, and age at vaccination. CONCLUSION: The recently approved 3-antigen vaccine is a cost-saving or cost-effective intervention for preventing HBV infection and addressing the long-standing burden of hepatitis B among US adults.

Brucellosis remains one of the most worldwide distributed zoonosis inflicting serious economical and human health problems in many areas of the world. The disease is caused by different species of the genus Brucella that have different tropisms towards different mammals being the most relevant for human health Brucella abortus, Brucella melitensis and Brucella suis that infect cows, goats/sheep, and swine respectively. For B. melitensis, considered the species with more zoonotic potential and highly aggressive for animals, only one vaccine is available to date in the market: Rev 1. This attenuated strain has the disadvantage that is has a very high residual virulence for animals and humans and, for this reason, it is applied by ocular instillation which is technically challenging in many productive settings. For this reason, the search for new vaccines for caprine and ovine brucellosis is an active topic of research. We describe here the construction of a novel highly attenuated vaccine strain (Bm Delta-pgm) that confers excellent levels of protection against B. melitensis in the mouse model of infection. This strain is a clean deletion of the phosphoglucomutase (pgm) gene that codes for a protein that catalyzes the conversion of glucose-6-P to glucose-1-P, which is used as a precursor for the biosynthesis of many polysaccharides, including the O-antigen of the lipopolysaccharide and cyclic beta glucans. Our results indicate that vaccination with Bm Delta-pgm induces a robust memory cellular immune response but no antibody production against the O-antigen. Cross protection experiments show that this new vaccine protects against B. abortus and B. suis raising the possibility that Bm Delta-pgm could be used as a universal vaccine for the most important Brucella species.

BACKGROUND: There are currently no COVID-19 vaccine assessment systems in Japan that allow for the active surveillance of both vaccinated and unvaccinated persons. Herein, we describe the development of Japan's first COVID-19 vaccine effectiveness and safety assessment system with active surveillance capabilities. METHODS: The Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study was developed as a multi-source database that links four data types at the individual resident level: Basic Resident Register (base population information), Vaccination Record System (vaccination-related information), Health Center Real-time Information-sharing System on COVID-19 (HER-SYS; information on COVID-19 occurrence), and health care claims data (information on diagnoses, hospitalizations, diagnostic tests, and treatments). These data were obtained from four municipalities. Individual residents were linked across the data types using five matching algorithms based on names, birth dates, and sex; the data were anonymized after linkage. To ascertain the viability of the VENUS Study's database for COVID-19 vaccine assessments, we examined the trends in COVID-19 vaccinations, COVID-19 cases, and polymerase chain reaction (PCR) test numbers. We also evaluated the linkage rates across the data types. RESULTS: Our multi-source database was able to monitor COVID-19 vaccinations, COVID-19 cases, and PCR test numbers throughout the pandemic. Using the five algorithms, the data linkage rates between the COVID-19 occurrence information in the HER-SYS and the Basic Resident Register ranged from 85·4% to 91·7%. CONCLUSION: If used judiciously with an understanding of each data source's characteristics, the VENUS Study can provide a viable data platform that facilitates active surveillance and comparative analyses for population-based research on COVID-19 vaccine effectiveness and safety in Japan.

BACKGROUND: Genital human papillomavirus (HPV) infection is the most prevalent sexually transmitted infection among young adults ages 15-25 years in the United States (US). Although HPV vaccines are recommended for individuals ages through 26 years, vaccine completion rates remain substantially low. METHODS: Accordingly, our study utilized a comprehensive - Theoretical Domains Framework (TDF) of behavior change to systematically identify facilitators and barriers to catch-up HPV vaccinations. Five databases - Medline, Embase, CINAHL, ERIC, and PsycINFO were searched from January 2009 to July 2019 for empirical studies using quantitative and qualitative methods to assess HPV vaccine uptake among males ages 18-26 years within US college and university settings. The TDF analytic process included a content analysis using the mixed deductive-inductive approach to extract, analyze and categorize data into TDF domains/themes and sub-themes. RESULTS: Overall, 17 studies were selected for data extraction. We identified eleven key TDF domains that influenced HPV vaccination behavior among college male students: 'knowledge' (82% of included studies), 'environmental context and resources' (53%), 'beliefs about consequences' (53%), 'unrealistic optimism' (50%) and 'pessimism' (6%), 'emotion' (50%), 'social influences' (50%), 'beliefs about capabilities' (41%), 'intention' (24%), 'reinforcement' (18%), 'social professional role and identity'(12%), and 'behavioral regulation' (12%). Barriers influencing HPV vaccine uptake included lack of knowledge and awareness regarding HPV infections, HPV vaccine safety, effectiveness, side effects, and costs; absence of health providers' recommendations; lack of healthcare and health insurance; low levels of perceived susceptibility and severity for HPV infections; HPV vaccine misinformation; as well as social stigma and peer influences regarding HPV vaccinations. Enablers for HPV vaccine uptake included high levels of perceived benefits for HPV vaccines. DISCUSSION: Our study theoretically identified factors influencing HPV vaccinations. This could inform the efficient planning, support, and implementation of interventions that facilitate catch-up HPV vaccination practices among high-risk males within college/university settings.

Vaccination is the most important strategy in preventing COVID-19. Vaccine efficacy and safety have been established in clinical trials but real-world data are useful to determine occurrence of adverse events in a population with heterogeneous characteristics. Knowledge on the hematologic events associated with different COVID-19 vaccines would be beneficial for patients as well as hematologists who oversee the care of these patients. This study aimed to determine the rates and outcomes of hematologic adverse events after COVID-19 vaccination in the Philippines. In this self-controlled case series, there were 268 individuals reported to have hematologic adverse events. Most received Comirnaty at 29.85%. Majority (62.31%) reported hematologic adverse events following the first dose of the vaccine. The overall event rate was 0.0182 per 10,000 vaccine doses; and lymphadenopathy was the most common hematologic adverse effect with a rate of 0.011 per 10,000 vaccine doses, followed by anemia at 0.0034 per 10,000 vaccine doses and thrombocytopenia at 0.0017 per 10,000 vaccine doses. Autoimmune cytopenias were also reported with an event rate of 0.0007 per 10,000 vaccine doses for ITP. One-hundred thirty two (49.25%) were fully recovered and 23.88% were recovering from hematologic adverse events as of the time of writing. The study showed a low rate of hematologic adverse events post COVID-19 vaccination with the seven different vaccine brands administered in the Philippines.

BACKGROUND: In the Danish childhood vaccination program, the human papillomavirus (HPV) vaccination coverage is lower than for other vaccines. To tailor a targeted HPV vaccination effort, we aimed to identify girls in Denmark with lower first dose HPV vaccination coverage than girls in general. METHODS: A population-based retrospective cohort study was performed of girls born in 2001-2004, residing in Denmark in September 2019 (N = 128,351). Data from the Danish Vaccination Register was linked to sociodemographic data from the Danish Civil Registration System and Statistics Denmark. Cox's proportional hazard regression models were used to compare vaccination uptake rates between subgroups of girls. RESULTS: HPV vaccination coverage at 14 years of age varied widely by municipality (53.4-80.6%). Girls living with neither of their parents had a lower chance of being vaccinated compared to girls living with both their parents (HR 0.43; 95% CI 0.41-0.46), likewise for girls attending special need education compared with girls attending public schools (HR 0.50; 95% CI 0.42-0.59). The vaccination uptake among immigrants was lower compared to Danish-born girls (HR 0.51; 95% CI 0.49-0.54), especially among immigrant girls whose parents had not passed any Danish exams. Finally, girls who were DTaP-IPV revaccinated had a 50% greater chance of being HPV vaccinated compared to girls who were not (HR 1.61; 95% CI 1.58-1.64). CONCLUSION: To increase the HPV vaccination uptake, we recommend vaccination efforts targeting girls living without any of their parents, girls attending special need education, immigrants, and girls who are not DTaP-IPV revaccinated. When targeting immigrants, the effort should focus on disseminating sufficient and understandable information about the Danish childhood vaccination program to the parents.

The population in rural southwest Alaska has been disproportionately affected by COVID-19. To assess the benefit of COVID-19 vaccines, we analyzed data from the regional health system. We estimated vaccine effectiveness (VE) during January 16-December 3, 2021, against symptomatic SARS-CoV-2 infection after a primary series or booster dose, and overall VE against hospitalization. VE of a primary series against symptomatic infection among adult residents was 91.3% (95% CI: 85.7, 95.2) during January 16-May 7, 2021, 50.3% (95% CI, 41.1%-58.8%) during July 17-September 24, and 37.0% (95% CI, 27.8-45.0) during September 25-December 3, 2021; VE of a booster dose during September 25-December 3, 2021, was 92.1% (95% CI: 87.2-95.2). During the overall study period, VE against hospitalization was 91.9% (95% CI: 85.4-95.5). COVID-19 vaccination offered strong protection against hospitalization and a booster dose restored protection against symptomatic infection.

OBJECTIVES: To report the safety and immunogenicity profile of a protein subunit vaccine (MVC-COV1901) compared to AZD1222 and mRNA-1273 when given as a third (booster) dose to individuals who have completed different primary vaccine regimens. METHODS: Individuals were classified according to their primary vaccine regimens, including two-dose MVC-COV1901, AZD1222, or mRNA-1273. A third dose of either half-dose MVC-COV1901, full-dose MVC-COV1901, standard-dose AZD1222, half-dose mRNA-1273 was administered in a 1:1:1:1 treatment ratio to individuals with an interval range of 84-365 days after the second dose. Endpoints included safety, humoral immunogenicity, and cell-mediated immune response on trial days 15 and 29. Exploratory endpoint included testing against variants of concern (Omicron). RESULTS: Overall, 803 participants were randomized and boosted - 201 received half-dose MVC-COV1901, 196 received full-dose MVC-COV1901, 203 received AZD1222, and 203 received half-dose mRNA-1273. Reactogenicity was mild to moderate, and less in the MVC-COV1901 booster group. Heterologous boosting provided the best immunogenic response. Boosting with mRNA-1273 in MVC-COV1901 primed individuals induced the highest antibody titers, even against Omicron, and cell-mediated immune response. CONCLUSIONS: Overall, MVC-COV1901 as a booster showed the best safety profiles. MVC-COV1901 as a primary series, with either homologous or heterologous booster, elicited the highest immunogenic response. CLINICALTRIALS: gov registration NCT05197153.

COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18-65 years. South Africa's first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs. VE against asymptomatic and symptomatic infection was 90.6% for WT, 6.7% for Beta and 77.1% for Delta. No cases of severe COVID-19 were documented ahead of unblinding. Safety was consistent with the interim analysis, with no new safety concerns identified. Notably, South Africa's Delta wave occurred ≥ 9 months after primary series vaccination, suggesting that primary series AZD1222 vaccination offers a good durability of protection, potentially due to an anamnestic response. Clinical trial identifier: CT.gov NCT04444674.

BACKGROUND: Vaccination is the best mode of protection against tick-borne encephalitis (TBE) and its sequelae. The duration of protection and the optimal interval of repeat booster doses are still debated. The current study evaluated the persistence of the antibody response 11-15 years after a first booster vaccination following different primary vaccination schedules with a TBE vaccine (Encepur Adults, manufactured by Bavarian Nordic, previously by GSK). METHODS: This phase IV, open-label, mono-centric extension study enrolled adults who had received (at ≥ 12 years of age) primary vaccination with one of three randomly assigned TBE vaccine schedules (rapid [group R], conventional [group C], or accelerated conventional schedule [group A]) followed by a booster dose 3 years later. The antibody response was measured annually from 11 to 15 years post-booster using a TBE virus neutralization test (NT). An NT titer of ≥ 10 was considered as a clinically meaningful threshold and surrogate for protection. RESULTS: In total, 194 participants were enrolled and included in the per-protocol set; 188 completed the study. The percentage of participants with an NT titer ≥ 10 was 100% in group R and 99.0% in group A at all visits and ranged from 100% (year 11) to 95.8% (year 15) in group C. NT geometric mean titers were similar in the three study groups (181-267 in group R, 142-227 in group C, 141-209 in group A). NT geometric mean titers also remained high among participants ≥ 50 years old (98-206) and ≥ 60 years old (91-191) across study groups and time points. CONCLUSIONS: This study showed neutralizing antibody persistence for at least 15 years after a first booster dose of the Encepur Adults TBE vaccine in all age groups evaluated, regardless of which primary vaccination schedule was given to adolescents or adults. Trialregistry: ClinicalTrials.gov: NCT03294135.

INTRODUCTION: Borno state in north-eastern Nigeria is the epicentre of the >10 years' insurgency activities that have affected the region since 2009, resulting in the destruction of health facilities, killing of health workers, massive population displacement and lack of access to populations to provide health services. This article demonstrates how the involvement of community informants from insecure areas (CIIA) to conduct polio surveillance in security-challenged settlements of Borno state contributed to the expansion of polio surveillance reach beyond polio vaccination reach. METHOD: In each of the 19 security compromised Local Government areas (LGAs) with community informants from insecure areas, Android phones enabled with Vaccination Tracking System (VTS) technology and Open Data Kit (ODK) mobile application were provided to capture geo-coordinates as evidence (geo evidence) for polio surveillance activity conducted. These geo evidence captured were uploaded and mapped to show insecure settlements reached with polio surveillance and those yet to be reached. RESULTS: A total of 3183 security compromised settlements were reached for polio surveillance between March 2018 and October 2019 with valid geo evidence, 542 of these security-compromised settlements had not been previously reached by any other intervention for polio surveillance or polio vaccination. CONCLUSION: The capturing of geo-coordinates as a proxy indicator of polio surveillance activity conducted by informants provided significant evidence of settlements reached for sustained polio surveillance even when a case of Acute Flaccid Paralysis (AFP) had not been reported from these settlements. Using the geo evidence captured by CIIA in insecure settlements, we have demonstrated the expansion of polio surveillance reach beyond polio vaccination reach in Borno state.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

A syringe for the long-term, room-temperature storage and injection of vaccines is described. Stabilisation was achieved by drying from a trehalose-containing buffer which formed an inert soluble glass distributed in the internal interconnected voids in an absorbent, compliant, reticulated, medical-grade, porous sponge. The sponge is stored inside the barrel of a syringe and the vaccines are re-solubilised by the aspiration of water. The syringe contains the sponge throughout the filling and drying processes in manufacture, and in transport, stockpiling and finally injection. The active vaccine is delivered to the patient in the normal injection process by depressing the plunger, which compresses the sponge to completely expel the dose. Full recovery of vaccine potency, after 7-10 months @ 45 °C, was shown by complete protection against supra-lethal doses of active toxins in immunised Guinea pigs.

PREVENT-19, the pivotal phase 3 trial of the Novavax adjuvanted, recombinant spike protein COVID-19 vaccine (NVX-CoV2373), demonstrated that the vaccine was well tolerated and efficacious (vaccine efficacy, VE = 90%) for the prevention of symptomatic COVID-19. In the trial, participants were randomly assigned in a 2:1 ratio to receive 2 doses of NVX-CoV2373 or placebo 21 days apart. Throughout the study, the predominant SARS-CoV-2 variant was alpha, but additional variants were in circulation (i.e., beta, gamma, epsilon, and iota). VE among the per-protocol efficacy analysis population was calculated according to pre-specified disease severity (mild, moderate, or severe) criteria, but the impact on the risk of COVID-19-associated hospitalization was not specifically investigated. During this analysis period (January 25, 2021, to April 30, 2021 [95 days]), 4 hospitalizations occurred among the 77 events analyzed for the primary endpoint using the per-protocol population, 0 among vaccine recipients and 4 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 28.8, 100). Among an expanded efficacy population, also identified post hoc, which included COVID-19-associated hospitalizations without a requirement for diagnostic polymerase chain reaction testing performed at the study central laboratory, 12 total hospitalizations were identified, 0 among vaccine recipients and 12 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 83.1, 100). These additional data from the PREVENT-19 trial provide relevant public health information concerning the attributes of NVX-CoV2373.

The incidence of cardiac adverse events following JYNNEOS vaccination for prevention of mpox is unknown, however the Advisory Committee on Immunization Practices states that people with underlying cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination. We conducted a retrospective cohort study of 2,126 patients who were vaccinated with at least 1 dose of JYNNEOS vaccine and searched the Kaiser Permanente Northwest databases, including the electronic health record, to evaluate for cardiac adverse events of special interest (AESI). After physician adjudication, there were 10 confirmed cardiac AESI for an incidence of 3.1 per 1000 doses (exact 95% CI, 1.5 to 5.7), however none of these events could be directly attributed to vaccination. This retrospective cohort study of JYNNEOS vaccination for prevention of mpox identified 10 cardiac events that all had alternative explanations; and no hospitalizations or serious adverse outcomes were attributed to vaccination.

BACKGROUND: Sabin strain inactivated poliovirus vaccine (hereinafter as "sIPV") has been marketed globally in recent years, and more data on its immune persistence are needed. METHODS: This is a phase IV, open-labeled, parallel-controlled observational study based on phase III clinical trial as required by the China National Medical Products Administration (NMPA). At least 450 subjects aged four years (48-54 months) who received four doses at 2, 3, 4 and 18 months of age of sIPV or wild strain poliovirus vaccine (wIPV) in phase III clinical trial enrolled at a 2:1 ratio and collected blood samples for neutralizing antibody testing. RESULTS: A total of 500 subjects of four years old (334 in the sIPV group and 166 in wIPV group) were finally enrolled. The seropositivity rates (≥1:8) of neutralizing antibodies against serotype I-III were all 100.00% in all participants, and the geometric mean titers (GMT) were 1117.33 vs. 337.77 against serotype I, 632.72 vs. 267.34 against serotype Ⅱ, 1665.98 vs. 923.02 against serotype III in the sIPV group and wIPV group respectively at 4 years old. The seropositivity rates and GMTs of neutralizing antibodies in the test group were non-inferior to that of the control group against all three serotypes at different time points (P < 0.0001). The antibody GMT experienced a 10-fold, 8-fold, and 7-fold decline for serotypes I, Ⅱ, and III in the sIPV group, and a 13-fold, 7-fold, and 7-fold decline in the wIPV group from one month after booster vaccination to 4 years old. CONCLUSIONS: The neutralizing antibody level is much higher than the seroprotection cutoff (≥1:8) among children of 4 years old who completed the four-dose vaccination of either sIPV or wIPV. Therefore, another booster vaccination is not recommended at 4 years old. Longer immune persistence observation is still ongoing. REGISTRATION: ClinicalTrials.gov Identifier: NCT04989231.

BACKGROUND: A maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is offered to all pregnant women in the Netherlands in their second trimester since December 2019. However, former studies solely investigated the socio-psychological factors that influence vaccine acceptance among pregnant women in the third trimester. We identified predicting factors for attitude, intention and acceptance of maternal Tdap vaccination during the second trimester of pregnancy. METHODS: As part of a large prospective cohort study, women early in pregnancy completed a questionnaire on determinants regarding acceptance of maternal Tdap vaccination between 20 and 24w of gestation. The vaccine was offered after completion of the questionnaire. A random forest model and Receiver Operating Characteristics (ROC) analyses were carried out to identify the factors most predictive for vaccine acceptance on the whole data set, and also in sensitivity analysis on a subset reflecting the annual nationwide 70% vaccination uptake. RESULTS: Among 1158 participants who were offered a Tdap vaccination between 20 and 24w of gestation, 1098 (94.8%) accepted and 60 (5.2%) rejected the vaccine. Random forest analyses identified intention as most predictive for acceptance, followed by attitude towards vaccination, beliefs regarding safety, risk perception of severity of side effects, moral responsibility, beliefs regarding effectiveness and risk perception of susceptibility of side effects, with a sensitivity of 100% and a specificity of 40%, for which this combination could be improved by the ROC analysis to 82% and 67%, respectively. The sensitivity analysis yielded an order of predictors that generally corresponded with the initial model. CONCLUSIONS: Intention, attitude, beliefs on safety and effectiveness, risk perception of side effects and moral responsibility were most predictive for maternal Tdap vaccine acceptance during the second trimester of pregnancy, in accordance with studies regarding third trimester vaccination. These should be discussed by healthcare professionals early in pregnancy to provide an informed choice towards vaccine acceptance.

BACKGROUND: Procedural anxiety was anticipated in children 5-11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway. METHODS: The Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child's support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5-11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message. RESULTS: Between 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs. CONCLUSION: A tailored COVID-19 vaccination program for children 5-11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.

BACKGROUND: Determining background rates of medical conditions identified as adverse events of special interest (AESI) that may occur following COVID-19 vaccination is important for contextualising and investigating potential vaccine safety signals. METHODS: We conducted a retrospective population-based cohort study using linked emergency department, hospitalisation and death data for 2017 and 2018 from Australia's most populous state, New South Wales. Incident cases of select neurological conditions, arterial or venous thromboembolic conditions, secondary thrombocytopenia, myocarditis/pericarditis, and unique events of anaphylaxis and generalised convulsions were identified using internationally agreed upon diagnostic (ICD-10) codes. State-specific rates per 100,000 person-years were calculated, with further stratification by age group and sex where clinically relevant to the condition, and the number of expected cases nationally in one and 6 weeks was estimated. RESULTS: Background rates of selected neurological conditions were low with the exception of generalised convulsions for which 1,599-1,872 cases were estimated nationally in a 1-week period in the absence of vaccination. Using a narrow case definition, rates of Guillain-Barré Syndrome (3.9 per 100,000 person-years) were higher than international rates reported elsewhere. Thromboembolic and cerebral venous sinus thrombosis event rates increased with age. Myocarditis occurred more commonly in males, and was highest in males aged 18-24 years, with an estimated 1-4 cases expected nationally in a 1-week period. CONCLUSIONS: Using routinely collected linked healthcare data provides localised estimates of background rates of new onset or periodic AESI which enables rapid estimation of observed-versus-expected rates of events reported following COVID-19 vaccination. This Australian-specific analysis contributes AESI background rates which can be compared with those from other countries to enhance understanding of geographic variability in the frequency of specific AESI in the absence of vaccination, and can be utilised for signal detection during program implementation.

BACKGROUND: To enhance the production and availability of influenza vaccines in different regions of the world is paramount to mitigate the global burden of this disease. Instituto Butantan developed and manufactured an embryonated egg-based inactivated split-virion trivalent seasonal influenza vaccine as part of a technology transfer partnership with Sanofi Pasteur. METHODS: This is a phase IV, randomized, double-blind, active-controlled, multicenter clinical trial including adults 18-60 and > 60 years recruited during the 2019 southern hemisphere influenza season. Subjects were randomized 1:1 to receive either the Sanofi Pasteur Trivalent Seasonal Influenza Vaccine (SP-TIV) or Instituto Butantan Trivalent Seasonal Influenza Vaccine (IB-TIV). Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination. RESULTS: 624 participants were randomized and vaccinated. In both intention-to-treat and per-protocol analysis, non-inferiority of the SP-TIV versus IB-TIV was demonstrated for the three influenza strains. In the per-protocol analysis, the SP-GMT/IB-GMT ratios for H1N1, H3N2, and B were 0.9 (95%CI, 0.7-1.1), 1.2 (95%CI, 1.0-1.4), and 1.1 (95%CI, 0.9-1.3), respectively. Across vaccination groups, the most common adverse reactions (AR) were limited to the injection-site, including pain and tenderness. The majority of the ARs were graded 1 and/or 2 and lasted less than one day. No serious adverse reaction was observed. CONCLUSION: This study demonstrated the non-inferiority of the immunogenicity of a single-dose of Instituto Butantan versus a single dose of the Sanofi Pasteur Seasonal Trivalent Influenza Vaccine in adults. Both vaccines were well tolerated and presented similar safety profiles.

INTRODUCTION: An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. METHODS: We conducted a retrospective observational cohort study of pregnant people ages 15-49 years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018. We used a time-dependent covariate Cox model with stabilized inverse probability weights applied to evaluate associations between Tdap vaccination during pregnancy and chorioamnionitis and preterm birth outcomes. We used Poisson regression with robust variance with stabilized inverse probability weights applied to evaluate the association of Tdap vaccination with adverse infant outcomes. We performed medical record reviews on a random sample of patients with ICD-10-CM-diagnosed chorioamnionitis to determine positive predictive values (PPV) of coded chorioamnionitisfor "probable clinical chorioamnionitis," "possible clinical chorioamnionitis," or "histologic chorioamnionitis." RESULTS: We included 118,211 pregnant people; 103,258 (87%) received Tdap vaccine during pregnancy; 8098 (7%) were diagnosed with chorioamnionitis. The adjusted hazard ratio for chorioamnionitis in the Tdap vaccine-exposed group compared to unexposed was 0.96 (95% CI 0.90-1.03). There was no association between Tdap vaccine and preterm birth or adverse infant outcomes associated with chorioamnionitis. Chart reviews were performed for 528 pregnant people with chorioamnionitis. The PPV for clinical (probable or possible clinical chorioamnionitis) was 48% and 59% for histologic chorioamnionitis. The PPV for the combined outcome of clinical or histologic chorioamnionitis was 81%. CONCLUSIONS AND RELEVANCE: Tdap vaccine exposure during pregnancy was not associated with chorioamnionitis, preterm birth, or adverse infant outcomes. ICD-10 codes for chorioamnionitis lack specificity for clinical chorioamnionitis and should be a recognized limitation when interpreting results.

BACKGROUND: Cervical cancer is a preventable disease caused by human papillomavirus (HPV). The HPV vaccine uptake in Japan has been slow since the Ministry of Health, Labour and Welfare suspended the recommendation for proactive HPV vaccination in 2013. In April 2022, Japan initiated catch-up vaccinations for women who missed the opportunity to receive the HPV vaccine. However, as of September 2022, very few women had received catch-up vaccination, raising concerns about vaccine hesitancy in the target population. It is necessary to understand the thinking and motivation of the target population to develop effective strategies to improve vaccination rates. Therefore, using cluster analysis, this study aimed to clarify the pattern of HPV vaccine hesitancy among the catch-up generations in Japan. METHODS: This descriptive study was based on an Internet survey completed by 3,790 women in Japan aged over 18 years who were eligible for catch-up vaccination and had not yet received an HPV vaccine. Participants were asked about their intention and thinking about the HPV vaccine and descriptive norms on vaccination intention. Cluster analysis using k-means clustering was performed to clarify these patterns. RESULTS: Cluster analysis revealed three hesitancy patterns: acceptance, neutral and refusal. The acceptance group, with high intention, comprised 28.2% of the participants, and students and a high-income level mainly dominated this group. The refusal group, with negative thinking and low intention, accounted for 20.1% and was more prevalent among workers and the unemployed. The neutral group, with neutral thinking and intention, accounted for 51.6%. The perceived effect of descriptive norms on vaccination intention was large in the acceptance group but small in the refusal group. CONCLUSION: HPV vaccine awareness promotion strategies must be based on the characteristics of each group and the different distributions of sociodemographic factors.

OBJECTIVE: To evaluate the effectiveness of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine containing five pertussis components (Tdap5; Adacel®, Sanofi) when given during pregnancy at preventing pertussis in infants less than 2 months of age. METHODS: The US Centers for Disease Control and Prevention (CDC), in collaboration with the Emerging Infections Program (EIP) Network, undertook a case-control study evaluating the effectiveness of Tdap vaccination in pregnancy against pertussis in infants less than 2 months of age based on data collected by the EIP Network from 2011 through 2014. The dataset from the CDC/EIP Network study was used to conduct this product-specific vaccine effectiveness analysis of Tdap5 vaccination in pregnancy to prevent disease in young infants. The main outcome of interest was vaccine effectiveness in infants whose pregnant parents were vaccinated with Tdap5 between 27 and 36 weeks' gestation, in accordance with the ideal timing for Tdap vaccination in pregnancy recommended by the US Advisory Committee on Immunization Practices. Odd ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression, and vaccine effectiveness was calculated as (1-OR) × 100 %. RESULTS: There were 160 infant pertussis cases and 302 matched controls included in this Tdap5-specific study. Tdap5 effectiveness in preventing pertussis in infants whose pregnant parents were vaccinated between 27 and 36 weeks' gestation was 92.5 % (95 % CI, 38.5 %-99.1 %). Effectiveness of Tdap5 against pertussis-related hospitalization in infants whose pregnant parents were vaccinated between 27 and 36 weeks' gestation could not be calculated due to lack of discordance among matched cases and controls. Vaccination of the parents after pregnancy or less than 14 days before delivery did not protect infants from pertussis. CONCLUSIONS: Tdap5 vaccination in pregnancy between 27 and 36 weeks' gestation is highly effective at protecting young infants from pertussis. STUDY REGISTRATION: ClinicalTrials.gov, NCT05040802.

INTRODUCTION: In 2021, the ten provinces in Canada enacted COVID-19 vaccine mandates that restricted access to non-essential businesses and services to those that could provide proof of full vaccination to decrease the risk of transmission and provide an incentive for vaccination. This analysis aims to examine the effects of vaccine mandate announcements on vaccine uptake over time by age group and province. METHODS: Aggregated data from the Canadian COVID-19 Vaccination Coverage Surveillance System (CCVCSS) were used to measure vaccine uptake (defined as the weekly proportion of individuals who received at least one dose) among those 12 years and older following the announcement of vaccination requirements. We performed an interrupted time series analysis using a quasi-binomial autoregressive model adjusted for the weekly number of new COVID-19 cases, hospitalizations, and deaths to model the effect of mandate announcements on vaccine uptake. Additionally, counterfactuals were produced for each province and age group to estimate vaccine uptake without mandate implementation. RESULTS: The times series models demonstrated significant increases in vaccine uptake following mandate announcement in BC, AB, SK, MB, NS, and NL. No trends in the effect of mandate announcements were observed by age group. In AB and SK, counterfactual analysis showed that announcement were followed by 8 % and 7 % (310,890 and 71,711 people, respectively) increases in vaccination coverage over the following 10 weeks. In MB, NS, and NL, there was at least a 5 % (63,936, 44,054, and 29,814 people, respectively) increase in coverage. Lastly, BC announcements were followed by a 4 % (203,300 people) increase in coverage. CONCLUSION: Vaccine mandate announcements could have increased vaccine uptake. However, it is difficult to interpret this effect within the larger epidemiological context. Effectiveness of the mandates can be affected by pre-existing levels of uptake, hesitancy, timing of announcements and local COVID-19 activity.

Aluminum adjuvant is a typical adjuvant that can promote humoral immune response, but it lacks the ability to effectively induce cellular immune response. The water-soluble N-2-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles (N-2-HACC NPs) can enhance humoral and cellular immune responses of vaccines. To enable aluminum adjuvant to induce cellular immunity, the composite nano adjuvant N-2-HACC-Al NPs were synthesized by the N-2-HACC and aluminum sulfate (Al2(SO4)3). The particle size and zeta potential of the N-2-HACC-Al NPs were 300.70 ± 24.90 nm and 32.28 ± 0.52 mV, respectively. The N-2-HACC-Al NPs have good thermal stability and biodegradability and lower cytotoxicity. In addition, to investigate the immunogenicity of the composite nano adjuvant, the combined inactivated vaccine against Newcastle disease (ND) and H9N2 avian influenza (AI) was prepared with the N-2-HACC-Al NPs as a vaccine adjuvant. The immune effect of the vaccine (N-2-HACC-Al/NDV-AIV) was evaluated by chicken in vivo immunization. The vaccine induced higher levels of serum IgG, IL-4, and IFN-γ than those of the commercial combined inactivated vaccine against ND and H9N2 AI. The levels of IFN-γ were more than twice those of the commercial vaccine at 7 days post the immunization. The N-2-HACC-Al NPs could be used as an efficient nano adjuvant to enhance the effectiveness of vaccine and have immense application potential.

Avian influenza virus (AIV) poses a great threat to the poultry industry and public health. However commercial vaccines only provide limited immunity due to rapid virus mutation and rearrangement. Here, we developed an mRNA-lipid nanoparticle (mRNA-LNP) vaccine expressing AIV immunogenic protein hemagglutinin (HA) and also assessed its safety and immune-protection efficacy in vivo. Specifically, its safety was tested by inoculation of SPF chicken embryos and chicks, and there showed no clinical manifestations and pathological changes in both. As for the immune efficacy, the antibody titers, IFN-γ production levels, and viral loads in various organs were analyzed. The results showed that chickens in the mRNA-LNP-inoculated groups produced higher specific antibody titers compared with that in the control group by hemagglutination inhibition (HI) test. Meanwhile, the ELISpot assay demonstrated that the expression of IFN-γ was markedly induced in the mRNA-LNP group, and the viral loads in multiple organs were decreased. In addition, HE shows no obvious pathomorphological changes in the lungs of the mRNA-LNP-inoculated group. While, there was severe inflammatory cell infiltration in the DMEM-treated group instead. Taken together, the vaccine prepared in this study was safe and could trigger potent cellular and humoral immune response to defend against virus infection.

BACKGROUND: The American Academy of Pediatrics recommends birth doses of vitamin K, erythromycin ointment, and the hepatitis B vaccine, but the relationship between birth medication administration and childhood immunization compliance is understudied. The objective of this study is to evaluate rates of newborn medication administration, and risk factors for refusal in military beneficiaries and determine the relationship between medication refusal and under-immunization at 15 months. METHODS: A retrospective chart review was completed for all term and late preterm infants born at Brooke Army Medical Center, San Antonio, TX, from January 1, 2016, to December 31, 2019. The electronic medical record was queried for birth medication administration, maternal age, active-duty status, rank, and birth order. Childhood immunization records were extracted for all patients who continued care at our facility. A patient was considered completely immunized if they had received at least 22 vaccines by 15 months: three doses of the hepatitis B vaccine [PediarixTM], two doses of the rotavirus vaccine [RotarixTM], four doses of the DTAP vaccine [PediarixTM and Acel-ImmuneTM], three doses of Haemophilus influenza B vaccine [PedvaxhibTM], four doses of pneumococcal [Prevnar 13TM], three doses of IPV [PediarixTM], one dose of measles, mumps, and rubella [MMRTM], one dose of varicella [VarivaxTM] and one dose of hepatitis A vaccine [HarvixTM]. RESULTS: Seven thousand one hundred and forty infants were included; 99.3% received vitamin K, 98.8% received erythromycin ointment, and 93.8% received the hepatitis B vaccine. Refusal of the erythromycin ointment and hepatitis B vaccine was associated with older maternal age and higher birth order. Childhood immunization records were available for 607 infants; 7.2% (n = 44) were under-immunized by 15 months, with no infants being non-immunized. Refusal of the hepatitis B vaccine (RR: 2.9 (CI 1.16-7.31)) only at birth was associated with a higher risk of being under-immunized. CONCLUSIONS: Refusal of the hepatitis B vaccine in the nursery is associated with a risk of being under-immunized in childhood. Obstetric and pediatric providers should be aware of this association for appropriate family counseling.

BACKGROUND: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series. METHODS: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. RESULTS: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. CONCLUSIONS: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.

INTRODUCTION: In order to evaluate trends in death after COVID-19 vaccination we analyzed the timing of death relative to vaccination date and the causes of death in vaccinated Utahns in 2021. METHODS: We matched people in the Utah immunization registry with documented COVID-19 vaccinations between December 18, 2020 and December 31, 2021 to Utah's 2021 vital statistics death records. Vaccinated people were categorized as having one, two, or ≥ three COVID-19 vaccine doses in a time-updated metric. We examined crude mortality rates by dosing groups in two-week intervals for all deaths, and by COVID-19 versus non-COVID-19 causes, within the 44 weeks following receipt of the most recent vaccine. RESULTS: We identified 2,072,908 individuals who received at least one dose of COVID-19 vaccine of whom 10,997 died in 2021. Only 17.5 % of the total vaccinated population was age 65+, while 80.9 % of those who died were over 65. In the four weeks following the first or second vaccination, all-cause mortality was low and then stabilized for the remainder of the evaluation period at a bi-weekly average of 33.0 and 39.0 deaths/100,000 people for one and two doses, respectively. Typical seasonal variation in death was observed among those with two doses. Small sample size precluded analysis of those with ≥ three doses, but trends were similar. CONCLUSIONS: Mortality rates in the 44 weeks following the COVID-19 vaccination did not show trends suggesting an increase in mortality related to COVID-19 vaccination, reinforcing the safety of COVID-19 vaccines. This represents an accessible approach for local evaluation.

BACKGROUND: World Health Organization approved vaccines have demonstrated relatively high protection against moderate to severe COVID-19. Prospective vaccine effectiveness (VE) designs with first-hand data and population-based controls are nevertheless rare. Neighborhood compared to hospitalized controls, may differ in compliance to non-pharmacuetical interventions (NPI) compliance, which may influence VE results in real-world settings. We aimed to determine VE against COVID-19 intensive-care-unit (ICU) admission using hospital and community-matched controls in a prospective design. METHODS: We conducted a multicenter, observational study of matched cases and controls (1:3) in adults ≧18 years of age from May to July 2021. For each case, a hospital control and two community controls were matched by age, gender, and hospital admission date or neighborhood of residence. Conditional logistic regression models were built, including interaction terms between NPIs, lifestyle behaviors, and vaccination status; the model's β coefficients represent the added effect these terms had on COVID-19 VE. RESULTS: Cases and controls differed in several factors including education level, obesity prevalence, and behaviors such as compliance with routine vaccinations, use of facemasks, and routine handwashing. VE was 98·2% for full primary vaccination and 85·6% for partial vaccination when compared to community controls, and somewhat lower, albeit not significantly, compared to hospital controls. A significant added effect to vaccination in reducing COVID-19 ICU admission was regular facemask use and VE was higher among individuals non-compliant with the national vaccine program, and/or tonroutine medical visits during the prior year. CONCLUSION: VE against COVID-19 ICU admission in this stringent prospective case-double control study reached 98% two weeks after full primary vaccination, confirming the high effectiveness provided by earlier studies. Face mask use and hand washing were independent protective factors, the former adding additional benefit to VE. VE was significantly higher in subjects with increased risk behaviors.

INTRODUCTION: Since the first COVID-19 messenger RNA vaccines became available globally for emergency or conditional use, post-marketing surveillance activities have been implemented for the monitoring of any adverse events that might arise in daily clinical practice and were not detected earlier during clinical trials. METHODS: Safety data concerning the BNT162b2 and the mRNA-1273 COVID-19 vaccines were collected from the Vaccine Adverse Event Reporting System (VAERS) for the period from December 2020 to October 15, 2021. In addition to a descriptive analysis of individuals who experienced an adverse event after vaccination, a case-non-case analysis was performed by using the Reporting Odds Ratio with 95 % confidence interval as statistical parameter for detecting differences in reporting rates between the two mRNA vaccines. RESULTS: At the cut-off date, a total of 758,040 reports were submitted to VAERS, of which 439,401 were related to the Pfizer-BioNTech (BNT162b2) vaccine and 318,639 to the Moderna vaccine (mRNA-1273). Most common adverse events following immunization for both mRNA vaccines were headache, fatigue, pyrexia, dizziness, nausea, pain, chills, and pain in extremity. A disproportionality was found for BNT162b2 as compared with mRNA-1273 for some events of special interest, such as myocarditis [ROR 2.00; 95 % confidence interval (CI), 1.93-2.06], Bell's palsy (1.34; 1.29-1.39), and anaphylactic shock (3.23; 2.96-3.53). CONCLUSION: Even if some rare adverse events were identified, our survey of post-marketing surveillance has provided further evidence of the favourable safety profile of mRNA vaccines.

OBJECTIVES: To study short and long-term disease activity and vaccine-related adverse events in a cohort of JIA patients who received the live attenuated measles-mumps-rubella (MMR) booster vaccine while being treated with immunosuppressive and immunomodulatory therapies. METHODS: A retrospective study was performed in the UMC Utrecht, clinical and therapeutic data were collected from electronic medical records for two visits before and two visits after the MMR booster vaccine of JIA patients. Drug therapy was collected and adverse events related to the vaccine were requested from the patients during clinical visits or by short phone interviews. Associations between MMR booster vaccination and the active joint count, physician global assessment of disease activity, patient-reported visual analogue scale (VAS) for well-being and clinical Juvenile Arthritis Disease Activity Score (cJADAS) were analyzed using multivariable linear mixed effects analyses. RESULTS: A total of 186 JIA patients were included in the study. At the time of vaccination, 51% of the patients used csDMARD and 28% used bDMARD therapy. Overall, adjusted disease activity scores after MMR booster vaccination were not significantly different compared to pre-vaccination. Mild adverse events related to the MMR booster were reported for 7% of the patients. No serious adverse events were reported. CONCLUSION: MMR booster vaccination was safe and did not worsen disease activity during long-term follow-up in a large cohort of JIA patients being treated with both csDMARDs and biological DMARDs.

INTRODUCTION: Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. MATERIALS AND METHODS: We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. RESULTS: Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. DISCUSSION: Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.

OBJECTIVE: We describe provider documented counseling patterns and perception regarding HPV vaccination among patients with a history of cervical dysplasia. METHODS: All patients ages 21-45 who underwent colposcopy at a single academic medical center from 2018 to 2020were sent a self-administered survey through the electronic medical record patient portal to assess their attitudes regarding human papillomavirus (HPV) vaccination. Demographic information, HPV vaccination history, and documented obstetrics and gynecology provider counseling at the time of colposcopy were examined. RESULTS: Of 1465patients, 434 (29.6 %) reported or had documented receipt of at least one dose of the human papillomavirus vaccine. The remainder reported they were not vaccinated or had no documentation of vaccination. Proportion of vaccinated patients was higher among White compared to Black and Asian patients (P = 0.02). On multivariate analysis, private insurance (aOR 2.2, 95 % CI 1.4-3.7) was associated with vaccinated status while Asian race (aOR 0.4, 95 % CI 0.2-0.7) and hypertension (aOR 0.2, 95 % CI 0.08-0.7) were less likely to be associated with vaccination status. Among patients with unvaccinated or unknown vaccination status, 112 (10.8 %) received documented counseling regardingcatch-up human papillomavirus vaccination at a gynecologic visit. Patients seen by a sub-specialist obstetrics and gynecologic provider were more likely to have documented provider counseling regarding vaccination compared to those seen by a generalist obstetric/gynecologist provider (26 % vs 9.8 %, p < 0.001). Patients cited lack of physician discussion (53.7 %) and the belief that they were too old to receive the HPV vaccine (48.8 %) as the main reasons for remaining unvaccinated. CONCLUSION: HPV vaccination and the rate of obstetric and gynecologic provider counseling regarding HPV vaccination among patients undergoing colposcopy remains low. When surveyed, many patients with a history of colposcopy cited provider recommendation as afactor in their decision to undergo adjuvant HPV vaccination, demonstrating the importance of provider counseling in thisgroup.

BACKGROUND: It has been claimed that COVID-19 vaccination is associated with excess mortality during the COVID-19 pandemic, a claim that contributes to vaccine hesitancy. We examined whether all-cause mortality has actually increased in Cyprus during the first two pandemic years, and whether any increases are associated with vaccination rates. METHODS: We calculated weekly excess mortality for Cyprus between January 2020 and June 2022, overall and by age group, using both a Distributed Lag Nonlinear Model (DLNM) adjusted for mean daily temperature, and the EuroMOMO algorithm. Excess deaths were regressed on the weekly number of confirmed COVID-19 deaths and on weekly first-dose vaccinations, also using a DLNM to explore the lag-response dimension. RESULTS: 552 excess deaths were observed in Cyprus during the study period (95% CI: 508-597) as opposed to 1306 confirmed COVID-19 deaths. No association between excess deaths and vaccination rates was found overall and for any age group except 18-49 years, among whom 1.09 excess deaths (95% CI: 0.27-1.91) per 10,000 vaccinations were estimated during the first 8 weeks post-vaccination. However, detailed cause-of-death examination identified just two such deaths potentially linked to vaccination, therefore this association is spurious and attributable to random error. CONCLUSIONS: Excess mortality was moderately increased in Cyprus during the COVID-19 pandemic, primarily as a result of laboratory-confirmed COVID-19 deaths. No relationship was found between vaccination rates and all-cause mortality, demonstrating the excellent safety profile of COVID-19 vaccines.

Vaccines are an essential tool for the control of viral infections in domestic animals. We generated recombinant vector herpesvirus of turkeys (vHVT) vaccines expressing computationally optimized broadly reactive antigen (COBRA) H5 of avian influenza virus (AIV) alone (vHVT-AI) or in combination with virus protein 2 (VP2) of infectious bursal disease virus (IBDV) (vHVT-IBD-AI) or fusion (F) protein of Newcastle disease virus (NDV) (vHVT-ND-AI). In vaccinated chickens, all three vHVT vaccines provided 90-100% clinical protection against three divergent clades of high pathogenicity avian influenza viruses (HPAIVs), and significantly decreased number of birds and oral viral shedding titers at 2 days post-challenge compared to shams. Four weeks after vaccination, most vaccinated birds had H5 hemagglutination inhibition antibody titers, which significantly increased post-challenge. The vHVT-IBD-AI and vHVT-ND-AI vaccines provided 100% clinical protection against IBDVs and NDV, respectively. Our findings demonstrate that multivalent HVT vector vaccines were efficacious for simultaneous control of HPAIV and other viral infections.

BACKGROUND: Despite the potential of geospatial technologies to track and monitor coverage, they are underutilized for guiding immunization program strategy and implementation, especially in low-and-middle-income countries. We conducted geospatial analysis to explore the geographic and temporal trends of immunization coverage, and examined the pattern of immunization service access (outreach and facility based) by children. METHODOLOGY: We extracted data to analyze coverage rates across different dimensions (by enrolment year, birth year and vaccination year) from 2018 till 2020 in Karachi, Pakistan using the Sindh Electronic Immunization Registry (SEIR). We conducted geospatial analysis to assess variation in coverage rates of BCG, Pentavalent (Penta)-1, Penta-3, and Measles-1 vaccines using Government targets. We also analyzed the proportion of children receiving their routine vaccinations at fixed centers and outreach and examined whether children received vaccinations at the same or multiple immunization centers. RESULTS: A total of 1,298,555 children were born, enrolled or vaccinated from 2018 till 2020. At the district level, analysis by enrollment and birth year showed coverage increased between 2018 and 2019 and declined in 2020, while analysis by vaccination year showed consistent increase in coverage. However, micro-geographic analysis revealed pockets where coverage persistently declined. Notably 27/168, 39/168 and 3/156 Union councils showed consistently declining coverage when analyzing by enrollment, birth and vaccination year respectively. More than half (52.2%, 678,280/1,298,555) of the children received all their vaccinations exclusively through fixed centers and, 71.7% (499,391/696,701) received all vaccinations from the same centers. CONCLUSION: Despite overall improving vaccination coverage between 2018 and 2020, certain geographic areas have consistently declining coverage rates, which is detrimental for equity. Making immunization inequities visible through geospatial analysis is the first step to ensure resources are allocated optimally. Our study provides impetus for immunization programs to develop and invest in geospatial technologies, harnessing its potential for improved coverage and equity.

The schools-based influenza vaccination programme has seen consistently high uptake in Wales, however coverage in pre-school two and three-year olds is lower. One health board area (Cwm Taf University Health Board (UHB)) developed an intervention to offer live attenuated influenza vaccine (LAIV) for three-year olds attending nursery schools alongside the existing general practice (GP) programme. During the pilot, sessions were delivered by health visitors, working with school nurses. The mixed delivery model led to vaccination data being recorded in two separate data systems. To evaluate the impact of the pilot on overall vaccine uptake, data linkage was carried out within the Secure Anonymised Information Linkage (SAIL) Databank. Overall influenza vaccine uptake was calculated for each health board in Wales for two and three-year olds for the 2015-16, 2016-17, and 2017-18 influenza programmes. Uptake in two-year olds in Cwm Taf UHB and also uptake in three-year olds in other health boards in Wales were the comparison groups. Uptake of influenza vaccine in the 2015-16 (pre-intervention) period was 41.0% for three-year olds in Cwm Taf UHB. Following the intervention, coverage increased to 70.7% and 71.5% for 2016-17 and 2017-18 respectively. The same increases in uptake were not seen in two-year olds in Cwm Taf UHB or in three-year olds in non-intervention health boards. In Cwm Taf UHB resident three-year olds in 2015-16 there was an inequality gap in the uptake of 17.4 percentage points between the most and least deprived areas. Uptake increased across all deprivation quintiles in 2016-17 and 2017-18; and the inequality gap decreased to 10.3 and 13.4 percentage points respectively. Influenza vaccination uptake and equality of uptake in three-year olds can be improved by adopting a mixed delivery model across nursery school based immunisation sessions with the additional option of influenza vaccination at GPs.

The live attenuated temperature sensitive vaccine strain MS-H (Vaxsafe® MS, Bioproperties Pty. Ltd., Australia) is widely used to control disease associated with M. synoviae infection in commercial poultry. MS-H was derived from a field strain (86079/7NS) through N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-induced mutagenesis. Whole genomic sequence analysis of the MS-H and comparison with that of the 86079/7NS have found that MS-H contains 32 single nucleotide polymorphisms (SNPs). Three of these SNPs, found in the obgE, oppF and gapdh genes, have been shown to be prone to reversion under field condition, albeit at a low frequency. Three MS-H reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE, oppF and gapdh (TS4), appeared to be more immunogenic and transmissible compared to MS-H in chickens. To investigate the influence of these reversions in the in vitro fitness of M. synoviae, the growth kinetics and steady state metabolite profiles of the MS-H reisolates, AS2, AB1 and TS4, were compared to those of the vaccine strain. Steady state metabolite profiling of the reisolates showed that changes in ObgE did not significantly influence the metabolism, while changes in OppF was associated with significant alterations in uptake of peptides and/or amino acids into the M. synoviae cell. It was also found that GAPDH plays a role in metabolism of the glycerophospholipids as well as an arginine deiminase (ADI) pathway. This study underscores the role of ObgE, OppF and GAPDH in M. synoviae metabolism, and suggests that the impaired fitness arising from variations in ObgE, OppF and GAPDH contributes to attenuation of MS-H.

In the past decade, camelid nanobodies have been developed for multiple applications, including immuno-imaging, cancer immunotherapy, and antiviral therapeutics. Despite the prevalence of these approaches, nanobodies have rarely been used to assess the potency of vaccine antigen candidates, which are primarily based on mAb binding approaches. In this work, we demonstrate that a nanobody-based ELISA method is suitable for characterization of a leading respiratory syncytial virus (RSV) vaccine candidate, RSVPreF3. This nanobody, F-VHH-L66, compares similarly with AM14, an antibody well-known to be specific for the prefusion form of the RSV surface fusion glycoprotein, RSV F. ELISA assays based on F-VHH-L66 were specific for the trimeric, prefusion form of RSV F, the antigen conformation that best generates neutralizing antibodies. Additionally, the F-VHH-L66-based ELISA proved accurate, linear, and stability-indicating. Statistical analysis of 65 independent F-VHH-L66-based ELISA experiments indicated assay performance similar to that of ELISA assays based on AM14. Moreover, the binding kinetics of F-VHH-L66 to RSVPreF3 are comparable to those of AM14 when measured by surface plasmon resonance (SPR). Finally, F-VHH-L66 neutralized RSV(A) with similar efficacy as AM14; this bioactivity data further supports its use as an alternative to AM14 for pre-fusion specific structural characterization of RSVPreF3.

The feared diarrheal disease cholera remains an important global health problem. Use of oral cholera vaccine (OCV) from a global stockpile against both epidemic and endemic cholera is a cornerstone in the World Health Organisations (WHOs) global program for "Ending cholera by 2030". Three liquid inactivated whole-cell OCVs (Dukoral®, ShancholTM, and Euvichol-Plus®) are WHO prequalified and have proved to be safe and effective. However, their multicomponent composition and cold-chain requirement increase manufacturing, storage and transport costs. ShancholTM and Euvichol-Plus® OCVs used in WHOs global vaccine stockpile also lack the protective cholera toxin B-subunit (CTB) antigen present in Dukoral®, which results in suboptimal efficacy. WHOs Global Task Force on Cholera Control (GTFCC) has identified a thermostable, dry formulation vaccine as a priority for further OCV development. We describe here the development of such a vaccine, based on a lyophilized mixture of a single strain of formalin-killed Hikojima bacteria together with a low-cost, recombinantly produced CTB. The new vaccine, which is easy and inexpensive to manufacture, could be stored for at least 26 months at 25 °C and for at least 8 months at 40 °C with preservation of cell morphology and with no loss of protective Ogawa and Inaba lipopolysaccharides or CTB. It also proved to be well tolerated and to have equivalent oral immunogenicity in mice as ShancholTM and Dukoral® OCVs with regard to both serum and intestinal-mucosal antibody responses.

We conducted a prospective cohort study of 20 patients with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS group, median age seven years, 70% male) and 34 healthy controls without such a history (CONTROL group, median age eight years, 38% male) aged 5-12 years, to assess the immunogenicity of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®). Patients received two doses of COVID-19 mRNA BNT162b2 vaccine (10 ug/dose) 21 days apart. Pre-vaccine anti-S SARS-CoV-2 IgG antibodies were measured on the day of the first dose and at the median of 23 days after the second dose. The study was conducted during the COVID-19 wave dominated by the Omicron variant of the virus. Anti-NCP SARS-CoV-2 IgG antibodies were measured twice to evaluate incidents of infection during the study period. Pre-vaccine quantification of both types of antibodies allowed us to differentiate patients into COVID-19 naive and previously infected in order to compare hybrid immunity with vaccine-induced immunity. Before vaccination, anti-S IgG serum geometric mean concentration (GMC) was 61.17 BAU/ml in the PIMS group and 24.97 in the CONTROL group, while post-vaccination GMC was 3879.14 BAU/ml and 3704.87 BAU/ml, respectively, and did not significantly differ between the groups. Hybrid immunity (regardless of PIMS history) resulted in a higher concentration of SARS-CoV-2 anti-S antibodies after vaccination. Four (20%) of the children in the PIMS group and 11 (32%) in the CONTROL group got infected with SARS-CoV-2 during the study period, yet all of them asymptomatically, and this event has not significantly altered post-vaccination anti-S titers. In conclusion, COVID-19 vaccination was highly immunogenic in children, including those with a history of PIMS-TS; hybrid immunity overperforms vaccine-induced immunity in terms of serological response in children. However, vaccination effectiveness in preventing SARS-CoV-2 infections in children should be further evaluated.

The COVID-19 vaccination program implementation in Ontario, Canada has spanned multiple years and is ongoing. To meet the challenges of the program, Ontario developed and implemented a new electronic COVID-19 immunization registry, COVaxON, which captures individual-level data on all doses administered in the province enabling comprehensive coverage assessment. However, the need for ongoing COVID-19 vaccine coverage assessments over a multi-year vaccination program posed challenges necessitating methodological changes. This paper describes Ontario's COVID-19 immunization registry, the methods implemented over time to allow for the ongoing assessment of vaccine coverage by age, and the impact of those methodological changes. Throughout the course of the vaccination program, four different methodological approaches were used to calculate age-specific coverage estimates using vaccination data (numerator) obtained from COVaxON. Age-specific numerators were initially calculated using age at time of first dose (method A), but were updated to the age at coverage assessment (method B). Database enhancements allowed for the exclusion of deceased individuals from the numerator (method C). Population data (denominator) was updated to 2022 projections from the 2021 national census following their availability (method D). The impact was most evident in older age groups where vaccine uptake was high. For example, coverage estimates for individuals aged 70-79 years of age for at least one dose decreased from 104.9 % (method B) to 95.0 % (method D). Thus, methodological changes improved estimates such that none exceeded 100 %. Ontario's COVID-19 immunization registry has been transformational for vaccine program surveillance. The implementation of a single registry for COVID-19 vaccines was essential for comprehensive near real-time coverage assessment, and enabled new uses of the data to support additional components of vaccine program surveillance. The province is well positioned to build on what has been achieved as a result of the COVID-19 pandemic and expand the registry to other routine vaccination programs.

Recent work demonstrating that asymptomatic carriers of P. falciparum parasites make up a large part of the infectious reservoir highlights the need for an effective malaria vaccine. Given the historical challenges of vaccine development, multiple parasite stages have been targeted, including the sexual stages required for transmission. Using flow cytometry to efficiently screen for P. falciparum gamete/zygote surface reactivity, we identified 82 antibodies that bound live P. falciparum gametes/zygotes. Ten antibodies had significant transmission-reducing activity (TRA) in a standard membrane feeding assay and were subcloned along with 9 nonTRA antibodies as comparators. After subcloning, only eight of the monoclonals obtained have significant TRA. These eight TRA mAbs do not recognize epitopes present in any of the current recombinant transmission-blocking vaccine candidates, Pfs230D1M, Pfs48/45.6C, Pf47 D2 and rPfs25. One TRA mAb immunoprecipitates two surface antigens, Pfs47 and Pfs230, that are expressed by both gametocytes and gametes/zygotes. These two proteins have not previously been reported to associate and the recognition of both by a single TRA mAb suggests the Pfs47/Pfs230 complex is a new vaccine target. In total, Pfs230 was the dominant target antigen, with five of the eight TRA mAbs and 8 of 11 nonTRA gamete/zygote surface reactive mAbs interacting with Pfs230. Of the three remaining TRA mAbs, two recognized non-reduced, parasite-produced Pfs25 and one bound non-reduced, parasite-produced Pfs48/45. None of the TRA mAbs bound protein on an immunoblot of reduced gamete/zygote extract and two TRA mAbs were immunoblot negative, indicating none of the new TRA epitopes are linear. The identification of eight new TRA mAbs that bind epitopes not included in any of the constructs currently under advancement as transmission-blocking vaccine candidates may provide new targets worthy of further study.

Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, the trimeric spike protein on the viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With the goal of generating a protein-based prophylactic, we designed a subunit vaccine comprising the recombinant S1 protein with a trimerization motif (S1-Fd) and examined its immunogenicity and protective immune responses in combination with various adjuvants. We found that sera from immunized wild-type and human DPP4 transgenic mice contained S1-specific antibodies that can neutralize MERS-CoV infection in susceptible cells. Vaccination with S1-Fd protein in combination with a saponin-based QS-21 adjuvant provided long-term humoral as well as cellular immunity in mice. Our findings highlight the significance of the trimeric S1 protein in the development of MERS-CoV vaccines and offer a suitable adjuvant, QS-21, to induce robust and prolonged memory T cell response.

BACKGROUND: V114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa-HBV-IPV/Hib and rotavirus RV1 vaccines. METHODS: V114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes. RESULTS: 1184 healthy infants 42-90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 μg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa-HBV-IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa-HBV-IPV/Hib and anti-rotavirus IgA geometric mean titers. CONCLUSIONS: After a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31.

The School Vaccination Check Program (SVCP) is a public health measure that aims to achieve high levels of National Immunization Program (NIP) vaccination coverage for children by checking the completion of the vaccination schedule for students when they enter elementary or middle school. Due to the COVID-19 pandemic, the SVCP was stopped in 2020 and 2021, and restarted in June-August 2022. In this study, we examined and quantified the relationship with SVCP and the vaccination uptake by comparing the vaccination coverage of 2021 and 2022. Based on the standard schedule, the vaccination records of DTaP5, IPV4, MMR2 and IJEV4 were evaluated for elementary school students. The Tdap6, IJEV5 and HPV1 were evaluated for the students from middle school. Using a difference-in-difference study design and national level big data, the study compared vaccination coverage as of August 2021 and 2022. The study found that the SVCP was effective in increasing vaccination coverage for targeted vaccinations such as DTaP5, IPV4, MMR2 and IJEV4 for elementary school students, and Tdap6, IJEV5 for middle school students. However, the SVCP did not show a statistically significant effect on increasing vaccination coverage on HPV1 for middle school students. School can play an important role to improve vaccination coverage. Therefore, close collaboration with health and education authority is crucial to accomplish successful vaccination program reducing vaccine preventable disease outbreaks in schools.

OBJECTIVES: Vaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC). METHODS: We fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022. RESULTS: For primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95-97) against Alpha, 87% (95%CI 84-88) against Delta and 31% (95%CI 25-37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86-89) against Delta and 68% (95%CI 65-70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62) respectively, 150-200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission. CONCLUSIONS: While we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.

In the wake of mass COVID-19 vaccination campaigns in 2021, significant differences in vaccine skepticism emerged across Europe, with Eastern European countries in particular facing very high levels of vaccine hesitancy and refusal. This study investigates the determinants of COVID-19 vaccine hesitancy and refusal, with a focus on these differences across Eastern, Southern and Western Europe. The statistical analyses are based on individual-level survey data comprising quota-based representative samples from 27 European countries from May 2021. The study finds that demographic variables have complex associations with vaccine hesitancy and refusal. The relationships with age and education are non-linear. Trust in different sources of health-related information has significant associations as well, with people who trust the Internet, social networks and 'people around' in particular being much more likely to express vaccine skepticism. Beliefs in the safety and effectiveness of vaccines have large predictive power. Importantly, this study shows that the associations of demographic, belief-related and other individual-level factors with vaccine hesitancy and refusal are context-specific. Yet, explanations of the differences in vaccine hesitancy across Eastern, Southern and Eastern Europe need to focus on why levels of trust and vaccine-relevant beliefs differ across regions, because the effects of these variables appear to be similar. It is the much higher prevalence of factors such as distrust of national governments and medical processionals as sources of relevant medical information in Eastern Europe that are relevant for explaining the higher levels of vaccine skepticism observed in that region.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but established complication of 1st dose ChAdOx1 nCoV19 vaccination (AZD1222), however this complication after dose 2 remains controversial. OBJECTIVES: To describe the clinicopathological features of confirmed cases of VITT post dose 2 AZD1222 vaccination in Australia, and to compare this cohort to confirmed cases of VITT post 1st dose. METHODS: Sequential cases of clinically suspected VITT (thrombocytopenia, D-Dimer > 5x upper limit normal and thrombosis) within 4-42 days of dose 2 AZD1222 referred to Australia's centralised testing centre underwent platelet activation confirmatory testing in keeping with the national diagnostic algorithm. Final classification was assigned after adjudication by an expert advisory committee. Descriptive statistics were performed on this cohort and comparative analyses carried out on confirmed cases of VITT after 1st and 2nd dose AZD1222. RESULTS: Of 62 patients referred, 15 demonstrated presence of antibody mediated platelet activation consistent with VITT after dose 2 AZD1222. Four were immunoassay positive. Median time to presentation was 13 days (range 1-53) platelet count 116x10^9/L (range 63-139) and D-dimer elevation 14.5xULN (IQR 11, 26). Two fatalities occurred. In each, the dosing interval was less than 30 days. In comparison to 1st dose, dose 2 cases were more likely to be male (OR 4.6, 95% CI 1.3-15.8, p = 0.03), present with higher platelet counts (p = 0.05), lower D-Dimer (p = 01) and less likely to have unusual site thromboses (OR 0.14, 95% CI 0.04-0.28, p = 0.02). CONCLUSIONS: VITT is a complication of dose 2 AZD1222 vaccination. Whilst clinicopathological features are less severe, fatalities occurred in patients with concomitant factors.

The widespread outbreak of the monkeypox virus (MPXV) recognized in 2022 poses new challenges for public healthcare systems worldwide. With more than 86,000 people infected, there is concern that MPXV may become endemic outside of its original geographical area leading to repeated human spillover infections or continue to be spread person-to-person. Fortunately, classical public health measures (e.g., isolation, contact tracing and quarantine) and vaccination have blunted the spread of the virus, but cases are continuing to be reported in 28 countries in March 2023. We describe here the vaccines and drugs available for the prevention and treatment of MPXV infections. However, although their efficacy against monkeypox (mpox) has been established in animal models, little is known about their efficacy in the current outbreak setting. The continuing opportunity for transmission raises concerns about the potential for evolution of the virus and for expansion beyond the current risk groups. The priorities for action are clear: 1) more data on the efficacy of vaccines and drugs in infected humans must be gathered; 2) global collaborations are necessary to ensure that government authorities work with the private sector in developed and low and middle income countries (LMICs) to provide the availability of treatments and vaccines, especially in historically endemic/enzootic areas; 3) diagnostic and surveillance capacity must be increased to identify areas and populations where the virus is present and may seed resurgence; 4) those at high risk of severe outcomes (e.g., immunocompromised, untreated HIV, pregnant women, and inflammatory skin conditions) must be informed of the risk of infection and be protected from community transmission of MPXV; 5) engagement with the hardest hit communities in a non-stigmatizing way is needed to increase the understanding and acceptance of public health measures; and 6) repositories of monkeypox clinical samples, including blood, fluids, tissues and lesion material must be established for researchers. This MPXV outbreak is a warning that pandemic preparedness plans need additional coordination and resources. We must prepare for continuing transmission, resurgence, and repeated spillovers of MPXV.

Parental refusal and delay of childhood vaccination has increased in recent years in the United States. This phenomenon challenges maintenance of herd immunity and increases the risk of outbreaks of vaccine-preventable diseases. We examine US county-level vaccine refusal for patients under five years of age collected during the period 2012-2015 from an administrative healthcare dataset. We model these data with a Bayesian zero-inflated negative binomial regression model to capture social and political processes that are associated with vaccine refusal, as well as factors that affect our measurement of vaccine refusal. Our work highlights fine-scale socio-demographic characteristics associated with vaccine refusal nationally, finds that spatial clustering in refusal can be explained by such factors, and has the potential to aid in the development of targeted public health strategies for optimizing vaccine uptake.

INTRODUCTION: The World Health Organization's Global Strategy on Human Resources for Health: Workforce 2030 sets policy recommendations and targets for in-service and pre-service training programs to improve workforce competency. To date, comprehensive reviews on immunization training have mainly focused on in-service trainings. This systematic review aimed to synthesize current literature on pre-service immunization training, including primary immunization competencies covered, methods used, outcomes on improving competencies and behavior change for immunization service delivery, and student readiness for immunization practice, in both low-resource and high-income settings. METHODS: A systematic search of seven scholarly databases identified published literature on pre-service training on immunization published between January 2001 and November 2021. It included all geographic regions and languages, study designs, and individuals preparing to enter the immunization workforce. Additional search methods included reviewing references of retrieved articles, scanning journals, and engaging pre-service training experts for unpublished reports. RESULTS: Search results yielded 5,611 articles; 39 articles met the inclusion criteria. Five articles were identified through other search methods. Studies took place mostly in high-income countries (35/44), targeted professional (medical, nursing, and pharmacy) students and tutors at health training institutions. Eight of the ten recommended immunization competencies were included in the curricula and methods used to deliver pre-service training varied. Teaching techniques and applied learning strategies using realistic situations increased students' knowledge, attitudes, and awareness of vaccine benefits; built confidence to administer vaccines and communicate with hesitant patients; and increased the likelihood of recommending vaccines. CONCLUSION: This review was the first step to understanding pre-service training on immunization. Further research is needed to inform pre-service training programs in low- and middle-income countries, particularly for nurses, vaccinators with low-level educational backgrounds, and other healthcare professional students. Prioritizing essential audiences, designing and delivering practical training, and evaluating results will help prepare students for the immunization challenges of tomorrow.

BACKGROUND: The World Health Organization has recommended a 4-dose schedule of the RTS,S/AS01 (RTS,S) vaccine for children in regions of moderate to high P. falciparum transmission. Faced with limited supply and finite resources, global funders and domestic malaria control programs will need to examine the relative cost-effectiveness of RTS,S and identify target areas for vaccine implementation relative to scale-up of existing interventions. METHODS: Using an individual-based mathematical model of P. falciparum, we modelled the cost-effectiveness of RTS,S across a range of settings in sub-Saharan Africa, incorporating various rainfall patterns, insecticide-treated net (ITN) use, treatment coverage, and parasite prevalence bands. We compare age-based and seasonal RTS,S administration to increasing ITN usage, switching to next generation ITNs in settings experiencing insecticide-resistance, and introduction of seasonal malaria chemoprevention (SMC) in areas of seasonal transmission. RESULTS: For RTS,S to be the most cost-effective intervention option considered, the maximum cost per dose was less than $9.30 USD in 90.9% of scenarios. Nearly all (89.8%) values at or above $9.30 USD per dose were in settings with 60% established bed net use and / or with established SMC, and 76.3% were in the highest PfPR2-10 band modelled (40%). Addition of RTS,S to strategies involving 60% ITN use, increased ITN usage or a switch to PBO nets, and SMC, if eligible, still led to significant marginal case reductions, with a median of 2,653 (IQR: 1,741 to 3,966) cases averted per 100,000 people annually, and 82,270 (IQR: 54,034 to 123,105) cases averted per 100,000 fully vaccinated children (receiving at least three doses). CONCLUSIONS: Use of RTS,S results in reductions in malaria cases and deaths even when layered upon existing interventions. When comparing relative cost-effectiveness, scale up of ITNs, introduction of SMC, and switching to new technology nets should be prioritized in eligible settings.

COVID-19 vaccination of U.S. children lags behind adult vaccination, but remains critical in mitigating the pandemic. Using a subset of a nationally representative survey, this study examined factors contributing to parental uptake of COVID-19 vaccine for children ages 12-17 and 5-11, stratified by parental COVID-19 vaccination status. Among vaccinated parents, uptake was higher for 12-17-year-olds (78.6%) than 5-11-year-olds (50.7%); only two unvaccinated parents vaccinated their children. Child influenza vaccination was predictive of uptake for both age groups, while side effect concerns remained significant only for younger children. Although parents were more likely to involve adolescents in vaccine decision-making than younger children, this was not predictive of vaccine uptake. These results highlight the importance of addressing the unique and shared concerns parents have regarding COVID-19 vaccination for children of varying ages. Future work should further explore adolescent/child perspectives of involvement in COVID-19 vaccination decision-making to support developmentally appropriate involvement.

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.

INTRODUCTION: Vaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership. METHODS: In June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analyses assessed predictors of subsequent vaccination among those initially unvaccinated. RESULTS: In June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9 %) became vaccinated by October 31, 2021. In June, unvaccinated participants were less likely to feel "very concerned" about getting COVID-19 than vaccinated participants (10.6 % vs. 43.3 %, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5 % reported vaccination before study end. Two latent factors predicted subsequent vaccination-being 'more receptive' was derived from motivation to protect one's own or others' health and resume usual activities; being 'less receptive' was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention. CONCLUSION: This study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions.

BACKGROUND: Hepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB-CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB-Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB-Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19). METHODS: HBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10mIU/mL received additional HepB-CpG or HepB-Eng doses. RESULTS: 147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups. CONCLUSIONS: Due to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng. CLINICALTRIALS: gov: NCT01282762.

According to evidence-based guidelines, vaccines against measles and varicella are generally recommended to susceptible HIV-positive patients, as long as they are not severely immunocompromised. However, routine screening to determine serologic status is not recommended. We conducted a seroprevalence study of anti-measles and anti-Varicella-Zoster virus (VZV) antibodies in adults living with HIV (PLWHA) consulting at Avicenne University Hospital in a Parisian suburb. Sera were collected in years 2018-2020 and tested by commercial immunoassays in 268 patients. Most of the patients were born in Sub-Saharan Africa (55 %) and only 23 % in Europe. Measles and varicella seropositivity were present respectively in 91.4 % and 96.2 % of patients. One patient in ten was seronegative to at least one of tested diseases. In the univariate analysis, only younger age (p = 0.027) was associated with a higher risk of measles seronegativity, while shorter time since arrival in France (p < 0.001) and shorter time since HIV discovery (p = 0.007) were associated with a higher risk of VZV seronegativity. In multivariate analysis no association was found. This study highlights the absence of specific risk factors for VZV and measles seronegativity in PLWHA and supports the importance of routine screening, in order to increase immunization rates and reduce risk of complications.

OBJECTIVES: To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS: 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS: BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS: BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.

Schmallenberg Virus (SBV), an arbovirus from the Peribunyaviridae family and Orthobunyavirus genus, was discovered in late 2011 in Germany and has been circulating in Europe, Asia and Africa ever since. The virus causes a disease associated with ruminants that includes fever, fetal malformation, drop in milk production, diarrhoea and stillbirths, becoming a burden for small and large farms. Building on previous studies on SBV nucleoprotein (SBV-N) as a promising vaccine candidate, we have investigated the possible protein regions responsible for protection. Based on selective truncation of domains designed from the available crystal structure of the SBV-N, we identified both the N-terminal domain (N-term; Met1 - Thr133) and a smaller fragment within (C4; Met1 - Ala58) as vaccine prototypes. Two injections of the N-term and C4 polypeptides protected mice knockout for type I interferon (IFN) receptors (IFNAR-/-) challenged with virulent SBV, opposite to control groups that presented severe signs of morbidity and weight loss. Viremia analyses along with the presence of IFN-γ secreted from splenocytes re-stimulated with the N-terminal region of the protein corroborate that these two portions of SBV-N can be employed as subunit vaccines. Apart from both proteinaceous fragments being easily produced in bacterial cells, the C4 polypeptide shares a high sequence homology (∼87.1 %) with the corresponding region of nucleoproteins of several viruses of the Simbu serogroup, a group of Orthobunyaviruses that comprises SBV and veterinary pathogens like Akabane virus and human infecting viruses like Oropouche. Thus, we propose that this smaller fragment is better suited for vaccine nanoparticle formulation, and it paves the way to further research with other related Orthobunyaviruses.

OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs). METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins. RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001). CONCLUSIONS: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.

OBJECTIVES: Characterize the public debate and discourse about vaccines during the covid-19 vaccination programmes. METHODS: We performed a manual content analysis of a sample of English-written Twitter posts that included the word vaccine and its derivatives. We categorized 7 variables pertaining to the content of the posts, and classified the type of user that published the post and the number of retweets. Then, the patterns of association between these variables were further explored. RESULTS: Among the tweets with negative tone towards vaccines, 33% display negationist discourses, 29% protest or defiance discourses, 13% discuss the pandemic management measures and yet another 13% of these tweets display a scientific discourse. Research results, vaccination data and practical information are more associated to positive tone towards vaccines, while news relate to neutral tone. The users that received more retweets were media accounts and journalists, followed by government accounts and scientific organizations related to the government. Tweets displaying preventive messages received more retweets in average. The discourses most associated with objective information are the preventive, institutional, medical-scientific, and those about the different measures to manage the pandemic. On the other hand, the most subjective tweets are those with negationist, antinegationist and protest discourses. CONCLUSIONS: Although there is a non-negligible proportion of tweets that are directly opposed to vaccines, also an important part of vaccine-negative content takes the form of protest discourses, criticisms towards government actions as well as towards the measures to tackle the pandemic. Therefore, negative discourses during the pandemic included serious vaccine hesitancy cases. Moreover, they were not only fuelled by distrust in science, but also and very importantly they were connected to dissatisfaction towards the public management of the pandemic.