Human Vaccines & Immunotherapeutics

BackgroundThe LP.8.1-containing COVID-19 mRNA vaccines were recommended for the 2025 seasonal vaccination campaigns in Europe and the United States. Safety data on these vaccines are limited. MethodsWe conducted a nationwide register-based cohort study in Denmark including all adults aged 65 years and older or at high risk of severe COVID-19 who had received previous COVID-19 vaccine doses. The study period was July 1, 2025, to December 3, 2025. We estimated incidence rate ratios using Poisson regression comparing rates of 30 adverse events within 28 days following LP.8.1-containing vaccination with reference period rates, adjusted for age, sex, region of residence, high risk of severe COVID-19, calendar time, and comorbidities. Self-controlled case series analysis was conducted as a complementary approach. ResultsAmong 1,565,697 individuals (mean age 69.5 years; 53.8% female), 958,633 received an LP.8.1-containing vaccine. Receipt of an LP.8.1-containing vaccine was not associated with a statistically significant increased rate of any of the 30 adverse events within 28 days after vaccination. The incidence rate ratio was 0.95 (95% CI, 0.86-1.06) for ischemic cardiac event, 0.83 (95% CI, 0.76-0.92) for cerebrovascular event, and 0.32 (95% CI, 0.04-2.50) for myocarditis. Results from the self-controlled case series analysis were similar. ConclusionsIn a nationwide cohort of more than 1.5 million adults, no increased risk of 30 adverse events was observed following vaccination with LP.8.1-containing COVID-19 mRNA vaccines.

Vaccine hesitancy emerged as a major challenge during the COVID-19 pandemic and has persisted beyond it, raising concerns about public readiness for vaccination in future pandemics. While extensive research has examined vaccine hesitancy for COVID-19 and routine immunization, it is unknown how the general population would respond to vaccination in a future pandemic, and what conditions might facilitate acceptance. Here, we analyzed data from a nationwide internet-based survey conducted in Japan between December 2024 and January 2025, involving 28,000 participants aged 15-84 years. We assessed intentions to receive vaccination in a hypothetical future pandemic under varying assumptions regarding disease fatality and vaccine immunity durability. Associations between vaccination intention and sociodemographic, psychological, health-related, informational, and infectious disease-related factors were examined. We further explored priority conditions that could increase vaccination intention. We found that only 53.1% of respondents indicated willingness to be vaccinated in a future pandemic with a case fatality rate comparable to COVID-19, representing a marked decline from observed COVID-19 vaccination coverage. Notably, 35.8% of individuals who had vaccinated during the COVID-19 pandemic reported hesitancy toward vaccination in a future pandemic. Higher assumed fatality rates and longer vaccine protection modestly increased willingness, particularly among those with ambivalent attitudes. Vaccination intention was lower among adults aged 20-40 years, women, individuals with lower income or education, and those endorsing misinformation or conspiracy beliefs, while higher infectious disease knowledge, greater fear of COVID-19, and active information seeking were associated with greater willingness. Clustering analysis identified eight distinct groups with heterogeneous priority structures. Free vaccination and clinical trial evidence were universally valued, whereas trust in authorities, domestic vaccine production, and convenience varied substantially across clusters. Public willingness to vaccinate in a future pandemic may be substantially lower than during COVID-19 and is shaped by diverse priorities. Tailored strategies and risk communication approaches that address heterogeneous concerns may be critical for strengthening preparedness for future pandemics.

ObjectiveAlthough COVID-19 vaccination is important for People Living with HIV given their elevated infection and comorbidity risks, some PLHIV are hesitant to accept vaccination. Hence, we conducted a cross-sectional study in British Columbia, Canada, aimed to identify socio-economic and health-related factors predicting COVID-19 vaccine uptake and contributing to hesitancy among PLHIV. MethodsA 34-item anonymous self-administered survey was disseminated to PLHIV accessing services through HIV and AIDS-related organisations e-newsletters between November 2022 and January 2023 in British Columbia. The survey included sociodemographic information, COVID-19 factors, HIV indicators, and the Vaccine Hesitancy Scale. Descriptive and inferential statistics were conducted to detect significant associations between the sociodemographic characteristics, health-related factors and COVID-19 vaccine uptake using IBM(R) SPSS(R) 28 and significance level at p<0.05. ResultsFrom the 276 respondents (mean age 29.93{+/-}7.55), 54.7% were men, 31.6% identified as sexual minorities, and 46.7% were of indigenous origin. Approximately 40% of the respondents received at least three vaccine doses, while 82.2% received at least one dose. Vaccine hesitancy was associated with lower education, age <44, and low income. Predictors of COVID-19 vaccine uptake included age [OR=1.06, 95% CI=1.01-1.12], bachelors degree [OR=0.22, 95% CI=0.07-0.72], family/friends infected with COVID-19 [OR 3.68 95% CI=1.56 - 8.67], HIV viral load >500 copies [OR=0.20, 95% CI=0.06-0.61], belief in vaccine importance [OR= 0.51, CI=0.28-0.95], trust in Health Canadas information [OR 0.49 CI=0.29-0.83], and concerns about vaccine adverse effects [OR=0.35, CI=0.22-0.56]. Concerns about vaccine adverse effects reduced the likelihood of receiving three COVID-19 vaccine doses by 65%. ConclusionsConsiderations must be taken around specific factors that may have an impact on COVID-19 vaccination rates among PLHIV, including information about vaccine adverse effects, HIV viral load, age, and education level. This insight should guide the development of policies and interventions aimed at encouraging individuals to maintain an up-to-date vaccination status.

BackgroundVaccine-preventable diseases pose significant health risks to older adults. Despite widespread vaccine availability, hesitancy related to uncertainty, misinformation, and access challenges continues to affect vaccination uptake, presenting an ongoing public health concern. ObjectiveThis study aimed to assess perceptions related to vaccination, develop age-appropriate educational strategies through community engagement, and evaluate changes in vaccine-related attitudes following an educational intervention among older adults in rural Delaware and Maryland. Study DesignA mixed-methods approach was employed, combining quantitative surveys with qualitative focus groups and interviews to examine vaccination-related perceptions and experiences. ParticipantsThe study included 124 participants prior to the intervention and 89 participants following the intervention. Participants were older adults residing in Sussex County (Delaware) and Somerset and Wicomico Counties (Maryland). AnalysisQuantitative data were analyzed using logistic regression, while qualitative data were analyzed thematically using inductive coding techniques. Comparisons between pre-and post-intervention findings examined changes in reported barriers, facilitators, perceptions, and confidence related to vaccination. ResultsPrior to the intervention, limited access to clear and reliable information (57.4%) and uncertainty toward public health guidance (36.8%) were commonly reported barriers, while family support and healthcare provider recommendations were identified as key facilitators. Following the intervention, reported barriers to vaccination decreased by 93%, and confidence in healthcare provider guidance increased by 190%. Educational materials were well received, with participants reporting improved understanding of vaccine effectiveness and safety, although some hesitation remained. ConclusionEducational interventions delivered through community-engaged approaches were associated with reduced barriers and increased confidence in vaccination among older adults. These findings highlight the value of targeted health education in supporting informed decision-making and suggest the need for continued public health efforts to sustain vaccine confidence. Further research is warranted to assess long-term outcomes and applicability across additional settings.

Background and objectiveVietnam had increasing rates of zero-dose children and sub-optimal COVID-19 vaccine booster coverage in 2022. With the Vietnamese Ministry of Health, we co-designed, implemented and evaluated a vaccine education and communication program for health workers and community leaders to improve trust, knowledge, communication skills and intention to vaccinate for routine childhood and COVID-19 vaccines. MethodThe Train-the-Trainer Vaccine Champions program was piloted in 2022 and deployed in 2023 in three low-coverage provinces. Master Trainers trained Provincial Trainers (healthcare workers and communication experts), who trained community leaders and other health workers as Champions to deliver community vaccine education sessions. Using mixed methods and the RE-AIM framework, we evaluated reach, effectiveness, adoption, implementation, and maintenance. Primary effectiveness outcomes included trust in vaccines and the healthcare system, vaccine knowledge, communication self-efficacy, satisfaction, and community respondents intention to vaccinate. Secondary outcomes included changes in Provincial level coverage pre- and 6-months post-intervention. ResultsThe program trained 56 Provincial Trainers (47% female), 286 Vaccine Champions (46% female), and reached 4027 community attendees. Communication self-efficacy and trust in vaccines and the health system increased significantly among Provincial Trainers and Vaccine Champions post-training but change in knowledge was minimal. Participants reported high satisfaction with sessions and materials and 86% of community respondents reported increased intention to vaccinate. Champions continue to run education sessions and promote other health programs with the Ministry of Health. ConclusionsIn Vietnam, a multi-level Vaccine Champions program that trained healthcare workers and community leaders to promote routine childhood and COVID-19 vaccination increased participant trust in vaccines and the health system, self-efficacy, and community intention to vaccinate. The program has potential to reduce healthcare workforce burden and has ongoing government support. Hybrid implementation-effectiveness trials are needed to determine impact on vaccine coverage and cost-effectiveness, alongside implementation outcomes, to guide scalability.

BackgroundBiological Es PNEUBEVAX 14(R) (BE-PCV14) is a WHO-prequalified 14-valent pneumococcal conjugate vaccine that adds emerging serotypes 22F and 33F to PCV13 coverage. We compared the safety and immunogenicity of a 3p+1 infant schedule of BE-PCV14 versus Prevenar 13(R) (PCV13) in Indian infants. MethodsIn this prospective, open-label, multicentre phase IV trial, PCV-naive infants aged 6-8 weeks received three primary doses of BE-PCV14 or PCV13 followed by a booster at 12-15 months. In the immunogenicity subset, serotype-specific IgG to the 14 vaccine serotypes and cross-protective 6A was measured 28 days post-booster. Endpoints were seroresponse rates (SRR defined as IgG [&ge;] 0.35 {micro}g/mL), IgG geometric mean concentrations (GMCs), and frequency of solicited / unsolicited adverse events (AEs) / serious AEs (SAEs) through 28 days post-booster. Post hoc non-inferiority of BE-PCV14 to PCV13 for all 14 serotypes was assessed by calculating the SRR differences and GMC ratios. For the SRR difference, non-inferiority was to be concluded if the lower limit of the 95% confidence interval was >-10%, and for the GMC ratio if the lower limit of the 95% confidence interval was >0.5. ResultsPost-booster immunogenicity was assessed in 559 BE-PCV14 and 147 PCV13 recipients. AEs occurred at similarly low frequencies in both groups ([~]6%), were mainly mild local reactions or pyrexia, and the two SAEs after BE-PCV14 were considered unrelated to vaccination. Post-booster SRRs with BE-PCV14 were [&ge;]92.8% for all 14 serotypes and >90% for 6A, comparable to PCV13 for shared serotypes. BE-PCV14 induced strong responses to the additional serotypes 22F and 33F, and post-booster/pre-booster GMC ratios were approximately 2.4-5.3 across serotypes. Post hoc analyses showed BE-PCV14 was non-inferior to PCV13 for all 14 serotypes by both SRR and GMC criteria. ConclusionsWhen used as a booster in a 3p+1 schedule, PNEUBEVAX 14(R) is well tolerated and elicits robust booster responses comparable to PCV13 while extending serotype coverage to 15 serotypes, including emerging 22F and 33F and cross-protective 6A.

Pneumonia remains a leading cause of global child mortality. Following the Pneumococcal Conjugate Vaccine (PCV) introduction in Yogyakarta, Indonesia, uptake for the primary series (PCV1 and PCV2) exceeded 90%. However, PCV3 coverage remained suboptimal (60% in 2023; 75% in 2024), indicating significant dropout. This study aimed to identify determinants of PCV immunization completeness and timeliness to address this gap. We conducted a cross-sectional study using cluster sampling among 405 caregivers of children aged 13-37 months in Yogyakarta City in March 2025. Data were collected via structured digital questionnaires assessing socio-demographics, perinatal conditions, knowledge, support systems, and attitudes toward multiple injections. Multivariate logistic regression was employed to determine factors associated with PCV immunization completeness and timeliness. Of 398 participants (98.3% response rate), the majority were female (95.7%) and housewives (75.1%). The prevalence of PCV completeness was 66.3%, while timeliness was only 36.4%. Multivariate analysis revealed that acceptance of multiple injections was the strongest predictor for both completeness (aOR 49.18; 95% CI: 21.30-113.50) and timeliness (aOR 22.04; 95% CI: 6.55-74.08). Additionally, home ownership (aOR 1.93; 95% CI: 1.04-3.58) was associated with completeness, whereas high knowledge (aOR 1.85; 95% CI: 1.12-3.03) improved timeliness. Conversely, preterm birth was significantly associated with lower odds of timeliness (aOR 0.29; 95% CI: 0.09-0.88). Acceptance of multiple injections emerged as the most critical modifiable factor for both outcomes. To optimize the PCV program, health authorities should prioritize counselling strategies to alleviate parental concerns regarding multiple injections. Additionally, intensified monitoring for preterm infants is crucial to mitigate immunization delays.

BackgroundThe number and timing of pneumococcal conjugate vaccine (PCV) primary doses can impact infant immune responses. This descriptive post hoc analysis evaluates the immunogenicity of the 20-valent PCV (PCV20) by vaccination timing in healthy infants in 2 key phase 3 trials. MethodsImmunogenicity endpoints from study B7471012 comparing PCV20 to 13-valent PCV (PCV13) in a 2+1 schedule were examined by timing of vaccination subgroup; the 2,4m subgroup (participants vaccinated at 2, 4, and 11-12 months of age), and the 3,5m subgroup (participants vaccinated at 3, 5, and 11-12 months). Additionally, immune responses from the 2+1 schedule were compared descriptively with those in study B7471011, in which participants received PCV20 or PCV13 in a 3+1 schedule at [~]2, 4, 6, and 12-15 months. ResultsSerotype-specific serum immunoglobulin G (IgG) responses in the PCV20 3,5m subgroup were higher than those in the 2,4m subgroup across all 20 vaccine serotypes and comparable to PCV13 immune responses in the 2,4m subgroup. Regardless of primary doses timing, PCV20 2+1 elicited strong immune responses after the toddler dose leading to post-toddler dose IgG levels similar to a 3+1 schedule. PCV20 was safe and well tolerated in both the 2,4m and 3,5 m subgroups. ConclusionsIn this descriptive analysis of the 2+1 schedule, a 1-month delay in PCV20 priming to 3 and 5 months was associated with improved immune responses comparable with those of PCV13 at 2 and 4 months. NCT04546425; NCT04382326.

ObjectivePregnant women are at higher risk of severe COVID-19, and vaccination significantly reduces the risk of severe infection. Despite its benefits, only 13% of pregnant women in the U.S. had received the updated 2024-25 vaccine by December 2024, with uptake varying across sociodemographic groups. This study examines perceptions on COVID-19 vaccination during pregnancy among U.S. adults enrolled in the Chasing Covid Cohort, analyzing responses across 16 surveys between March 2020 and December 2023 (N=4488). MethodsKey variables included sociodemographic characteristics, susceptibility to severe COVID-19 disease, perceived worry about COVID-19, individual and household vaccination status, symptoms of anxiety and depression, trusted information sources, and having a regular healthcare provider. Perceptions of vaccine safety and efficacy during pregnancy were measured using five Likert-scale statements, categorized into agreement, uncertainty, and disagreement. Exploratory factor analysis identified two constructs--safety and efficacy--which were analyzed in relation to participant characteristics using bivariate analysis and chi-square tests, and multivariable robust Poisson regression models. ResultsAmong all respondents and women of reproductive age, less than half (40%) perceived the COVID-19 vaccine as safe during pregnancy, and just over half recognized its efficacy. Individuals with a personal physician and those who trusted public health institutions or healthcare providers were more inclined to agree with the vaccines safety and efficacy. ConclusionsThese findings highlight the influence of demographic factors on vaccine perceptions, the potential impact of social networks during pregnancy, and the critical role of trust in public health institutions in promoting vaccine uptake.

Routine childhood immunization is still a critical topic for global public health, since it prevents an estimated 3.5 to 5 million deaths annually. However, its access remains uneven, especially in low-income countries, where structural inequalities limit the reach of immunization programs, and the Covid-19 pandemic disrupted routine services, worsening the existing disparities. This ecological study (2010-2023) examined associations between vaccine coverage and infant mortality using the WHO/UNICEF data for six childhood vaccines: BCG, DTP3, HepB3, Hib3, MCV2, and Pol3. Countries were stratified by income level using the World Bank World Development Indicators. Associations between vaccine coverage and infant mortality were evaluated using multivariable linear regression models adjusted for national income level. In addition, non-linear relationships and rank-based associations were explored using LOESS smoothing and Spearman correlation analyses. Results showed higher coverage and lower mortality in high-income countries; meanwhile, low-income countries faced both reduced coverage and higher mortality rates. A significant decline in coverage occurred in 2020, with only partial recovery by 2023. After adjusting for income, most vaccine coverage indicators lost statistical significance in relation to infant mortality. These findings highlight that income-related structural inequities determine immunization coverage and preventable child mortality, emphasizing the need for policies that simultaneously expand vaccine access, reduce structural barriers, and strengthen health systems.

BackgroundThe SARS-CoV-2 LP.8.1 subvariant was incorporated into the 2025-2026 U.S. COVID-19 vaccines (mRNA-1273.251 and mRNA-1283.251). We evaluated immunogenicity and safety of these vaccines against vaccine-matched and emerging variants in individuals aged [&ge;]65 and those aged 12-64 years at high-risk of severe COVID-19. MethodsData were generated from: (1) two independent, ongoing, phase 3b/4, open-label, single-arm studies in which participants received a single dose of 50-{micro}g mRNA-1273.251 (n=103; median age, 64.0 years) or 10-{micro}g mRNA-1283.251 (n=172, median age, 59.0 years) and followed through Day 29 post-vaccination; neutralizing antibodies (nAb) were measured at baseline (Day 1) and Day 29 using a pseudovirus neutralization assay against the vaccine-matched LP.8.1 variant; (2) Day 29 immunogenicity against circulating variants (BA.3.2.2, XFG, and NB.1.8.1) was assessed in a randomly selected subset; and (3) immune-escape potential was estimated using predictive modeling. Unsolicited adverse events (AEs), including serious AEs, leading to study withdrawal, and those of special interest, were monitored. ResultsBoth vaccines elicited robust nAbs at Day 29 against LP.8.1 (geometric mean fold-rise from baseline: 12-64 years, mRNA-1273.251, 26.3; mRNA-1283.251, 53.0; [&ge;]65 years, mRNA-1273.251, 15.4; mRNA-1283.251, 36.7) and circulating variants. Model-based estimates with mRNA-1273.251 were consistent with clinical data and indicated the highest responses against LP.8.1 and lower responses against BA.3.2.2. No vaccine-related AEs were reported in either study. ConclusionsmRNA-1273.251 and mRNA-1283.251 were well tolerated through Day 29 and elicited robust nAbs against vaccine-matched and circulating variants. In predictive models, BA.3.2.2 had the highest relative risk of immune escape following mRNA-1273.251 vaccination. SUMMARYLP.8.1-containing mRNA-1273.251 and mRNA-1283.251 vaccines given as a single dose were well tolerated and induced robust Day 29 neutralizing antibodies against LP.8.1 and circulating variants.

BackgroundCOVID-19 vaccine hesitancy remains a public health issue despite the fact that vaccines are readily available and recommended for all persons aged [&ge;]5 years in the United States. We aimed to describe parents plan to vaccinate their children in two different populations: families in a prospective, longitudinal cohort study and families experiencing homelessness enrolled in cross-sectional surveillance for acute respiratory infections. MethodsParticipants were parents/guardians of children aged <18 years, recruited either from a serial cross-sectional homeless study in Seattle-King County, Washington or from a household cohort study in the Seattle Metropolitan area. Participants were surveyed during October 2020--May 2021 about their plans to vaccinate their child against COVID-19. Vaccine plans were described by study population as well as by sociodemographic features and over time. ResultsAmong parents of 640 children enrolled in the household study surveyed in October 2021, 66% reported planning to vaccinate their child vaccinated against COVID-19 once vaccines became available. This proportion increased slightly over the study period, to 75% in May 2021. In the homeless study, 1284 surveys were collected from parents of 338 children. The proportion of parents of families experiencing homelessness who planned to have their child vaccinated against COVID-19 ranged from 52% in November 2020 to 16% in March 2021. ConclusionCOVID-19 vaccine plan among parents of children experiencing homelessness in Seattle-King County decreased over time, with the majority of parents reporting that they did not plan or were undecided about COVID-19 vaccination for their children by May 2021. Further investigations are needed among families experiencing homelessness to assess vaccine attitudes and perceived barriers to getting their children vaccinated against COVID-19. SummaryPlans to get vaccinated against COVID-19 was less common in children experiencing homelessness and intent decreased over time during the study, whereas vaccination was acceptable in other families in Seattle, WA

BackgroundInitial reports from the Netherlands indicate a decline in routine childhood vaccination uptake during and after the COVID-19 pandemic, with emerging evidence of reduced parental vaccine confidence. This study aimed to evaluate the long-term impact of the COVID-19 pandemic on routine childhood vaccination uptake. MethodsWe conducted a retrospective nationwide cohort study including all children born in the Netherlands in 2016-2024. First-dose DTaP-IPV vaccination status by age six months was obtained from the national immunisation register. National trends in vaccination uptake across pre-pandemic, pandemic, and post-pandemic periods were assessed using interrupted time series analyses. To further assess the independent effect of the pandemic, a matched-sibling analysis compared vaccination uptake within families before, during and after the pandemic. ResultsInterrupted time series analyses showed significant immediate decreases in vaccination uptake both at the start and end of the pandemic, accompanied by a continuing downward trend during the pandemic (OR 0.984, 95%CI 0.982-0.985) that further declined after its end (OR 0.995, 95%CI 0.994-0.997). In the matched-sibling analysis children eligible during and after the pandemic had lower odds of being vaccinated (pandemic: OR 0.66, 95%CI 0.55-0.80; post-pandemic: OR 0.20, 95%CI 0.17-0.25) compared to their pre-pandemic siblings. Also, later birth order was associated with lower odds compared to first-born siblings (second-born: OR 0.42, 95%CI 0.37-0.48). ConclusionsBoth analyses indicate a negative impact of the COVID-19 pandemic on parental vaccination decisions, which may reflect lingering pandemic effects or new post-pandemic factors, highlighting the need for further research into the drivers of vaccination uptake changes in the post-pandemic era.

Pregnant individuals have a greater susceptibility to severe disease from the coronavirus 2019 disease (COVID-19). Pregnant people also tend to be vaccine-hesitant, which is even more pronounced in certain racial and ethnic minority groups. The study objective was to determine whether social media ads promoting COVID-19 vaccination could influence vaccination likelihood among pregnant and recently pregnant participants who self-identified as Black or African American. Participants were interviewed individually or in focus groups to explore their attitudes about vaccination and to ask them to rate their COVID-19 vaccination likelihood after seeing a panel of ads featuring different messengers (e.g., doctor, peer, elder, faith leader) and content types (e.g., social proof, text-heavy, fear-based, activation). Ad ratings were analyzed using linear mixed models to examine the effect of vaccination status, ad messenger, and ad content type. Interviews were coded and analyzed for qualitative themes. Ad scores differed significantly by vaccine status, with vaccinated participants rating ads as more likely to inspire vaccine uptake, while unvaccinated participants rated ads negatively. No specific messenger or content type was rated as more probable to motivate vaccination. There was a significant interaction between faith-based messengers and COVID-19 vaccination status, with faith leaders perceived as more favorable by unvaccinated participants (p=0.008). Vaccine-hesitant respondents cited mistrust of healthcare providers and fears of medical racism. Although we did not identify content types that might be helpful in a public health vaccine campaign targeting Black pregnant people, faith leaders may be a trusted messenger for unvaccinated individuals.

BackgroundVaccination is a key measure to prevent severe influenza in adults aged [&ge;]80 years, who experience the highest burden of respiratory and cardiovascular complications. Because immunosenescence reduces the effectiveness of standard-dose vaccines (SD-IIV), enhanced formulations such as high-dose vaccines (HD-IIV) are recommended in the elderly. Real-world data on their effectiveness in adults aged [&ge;]80 years remain scarce. AimTo quantify the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV in preventing severe influenza disease in adults aged [&ge;]80 years. MethodsRetrospective, population-based cohort study conducted in Andalusia, Spain, during the 2024-2025 influenza season, including 279,649 vaccinated adults aged [&ge;]80 years. Data on sociodemographic characteristics, influenza vaccines, chronic diseases and clinical outcomes were taken from the Andalusian health population database. We used a directed acyclic graph to illustrate the assumed relationships between variables. The rVE of HD-IIV versus SD-IIV was estimated using augmented inverse probability weighting models. ResultsCompared with SD-IIV, HD-IIV was associated with a lower risk of hospitalization for influenza (rVE=34.0%; 95% CI=15.8-52.2). HD-IIV also showed improved effectiveness against laboratory-confirmed influenza (rVE=43.1%; 95% CI=24.6-61.7), hospitalization for acute myocardial infarction (rVE=26.4%; 95% CI=5.6-47.2), for stroke (rVE=32.9%; 95% CI=17.4-47.4), for pulmonary embolism (rVE=26.7%; 95% CI=0.7-52.6) and for overall cardiovascular outcomes (rVE=6.6%; 95% CI=0.9-12.2). No association was observed for hospitalization due to pneumonia, influenza/pneumonia, heart failure, respiratory outcomes, or in-hospital mortality. ConclusionAmong adults aged [&ge;]80 years, HD-IIV was more effective than SD-IIV in preventing hospitalization for influenza and severe cardiovascular outcomes, supporting its use in this at-risk population.

BackgroundVaccine hesitancy is a growing issue that the WHO ranks as one of the top 10 threats to global health. Public confidence in vaccines and rates of routine childhood vaccination have been declining around the world since the pandemic, when many countries saw the instatement of COVID-19 vaccine mandates. ObjectivesWe leveraged the COVID-19 add-on study, conducted by the CHILD Cohort Study (Canadas most phenotypically diverse, large prospective longitudinal birth cohort), to determine characteristics associated with adult participants vaccine hesitancy. Our goal was to identify potential strategies for addressing vaccine uptake concerns. This study complements others by examining more behavioural, socioeconomic, attitudinal and additional characteristics, in some cases with greater granularity, and by further exploring the effects of COVID-19 vaccine mandates on vaccine uptake and beliefs. MethodsWe generated penalized logistic regression models and used statistical tests to analyze a dataset of nearly 700 questionnaire responses where vaccine hesitancy was measured by participants agreement or disagreement with the following statements: "Getting myself vaccinated is important for the health of others in my community" and "Getting vaccinated is a good way to protect myself from disease. We also examined whether vaccination status or opinions changed after the imposition of vaccine mandates. ResultsWhile vaccine mandates were successful in increasing COVID-19 specific vaccine uptake in hesitant individuals vs confident individuals, they were ineffective in modifying hesitant individuals beliefs about vaccines. Vaccine-confident individuals were more likely to engage in pandemic safety measures such as physical distancing, while vaccine-hesitant individuals were more likely to have or had chronic medical conditions in the past, experience economic precarity, have lower socioeconomic status and/or formal education level, have had difficulty accessing medical care, and rely on friends and internet sites that were not governmental for COVID-19 related information. ConclusionsTo ensure that relevant information regarding vaccines reaches all segments of the population, outreach strategies should be tailored to individuals with a variety of cultural or educational backgrounds. Improving access to medical care could also improve access to reliable information. Vaccine mandates do not impact an individuals beliefs in vaccines, and so countering vaccine hesitancy itself is likely to be more effective in terms of ensuring continuous vaccine uptake in a population.

BackgroundIndia bears the worlds highest cervical cancer burden, yet awareness and uptake of the effective HPV vaccine remain low. Although Kerala has initiated pilot HPV vaccination programmes, stakeholder knowledge, attitudes, and practices (KAP) are not well documented. This pilot study aimed to assess the feasibility of a KAP study and to identify gaps in the questionnaire, for future analytical modelling. MethodsA cross-sectional pilot study was conducted in a school in Pulinkunnu, Kerala, among students aged 11-15 years, their parents, and teachers. A structured, validated questionnaire, developed in English, translated into Malayalam, was administered during school hours. Responses were entered into secure electronic spreadsheets. Descriptive statistics summarised KAP outcomes. As key demographic and behavioural predictors--such as gender, socioeconomic status, prior health education, and exposure to HPV information--were not captured, multivariable analysis was not undertaken. ResultsThe pilot included 75 students and 20 teachers, predominantly female. HPV-related knowledge was low across groups, with widespread misconceptions and limited awareness of vaccine availability and cervical cancer screening. Attitudes toward vaccination were mixed, marked by safety concerns and modest willingness to receive or recommend the vaccine. Practices reflected low prior awareness and uptake, with few respondents having heard of or received the HPV vaccine. ConclusionsThis pilot revealed major gaps in HPV-related knowledge, attitudes, and practices, among stakeholders and highlighted the need for an improved questionnaire in item clarity, response patterns, and missing variables and a larger study to identify predictors and inform targeted school-based HPV education efforts. Ethics and DisseminationEthical approval for this pilot study was obtained from the Institutional Ethics Committee of Pushpagiri Institute of Medical Sciences and Research Centre. Written informed consent was obtained from participating teachers, and parental consent was sought for students; however, parents were unavailable on the day of data collection, resulting in their non-participation. Verbal assent was obtained from all student participants prior to survey administration. Patient and Public InvolvementStudents, teachers, and parents were not involved in the development of the research protocol or the pilot questionnaire. As this was a preliminary feasibility study, no direct involvement in interpreting or disseminating the results is planned at this stage. Insights from the pilot will instead be used internally by the research team to refine the study tools and procedures for the full-scale investigation.

BackgroundEarly observational studies reported substantial reductions in all-cause mortality, suggesting that childhood vaccines might influence health in ways beyond their targeted disease. Such Non-Specific Effects (NSEs) of vaccines could potentially have important implications for the Expanded Programme of Immunization (EPI). In 2014 World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) commissioned a review of the NSE evidence, which called for more Randomized Controlled Trials (RCTs). We aimed to review all RCTs published after this WHO-commissioned review. MethodsFollowing PRISMA guidelines, we searched systematically for RCTs published during 2012-2025. Inclusion criteria: children under 5 years and all-cause mortality as the primary outcome for any vaccine intervention. Risk estimates were pooled using a random effects model, reflecting the underlying hypothesis: that live-attenuated vaccines greatly reduce, and inactivated vaccines increase all-cause mortality. ResultsWe identified seven RCTs that fit the inclusion criteria, all of them of live-attenuated vaccines (Bacillus Calmette-Guerin, measles, and oral polio vaccine). In total, 52,596 participants were included across these studies. Five were conducted in Guinea-Bissau, one in Guinea-Bissau and Burkina Faso, and one in India. The RCTs were not blinded, and no placebo was used, consistent with a moderate risk of bias. Our meta-analysis found no significant evidence of NSEs (vaccine effectiveness 5%; -16% to 22%). One study of low birthweight newborns admitted to neonatal intensive care units in India found a small but statistically significant NSE (17%; 2% to 31%); interestingly the effect primarily played out in the first 3 days of the study, raising concern of bias. DiscussionThe meta-analysis of seven RCTs of live-attenuated vaccines found no evidence of significant NSE on all-cause mortality. This was also true when adding RCTs from before 2012 studying NSEs. In conjunction with the WHO-SAGE review, the current body of evidence on NSEs on all-cause mortality does not warrant a paradigm shift, nor does it provide a rationale for changing vaccine programs.

Since the cessation of real-time monitoring of COVID-19 hospitalizations in early 2024, the burden of and vaccine effectiveness (VE) against severe COVID-19 in the Netherlands was largely unknown. Recently, hospitalization data from 2024 were made available for the purpose of monitoring and evaluating the COVID-19 vaccination campaigns. These data were linked to the population registry, vaccination registry and healthcare use data (for classification into medical risk groups). We analyzed the number and incidence of COVID-19 hospitalizations in 2023 and 2024 by age and medical risk group. VE against hospitalisation of the autumn booster of 2023 (by time since vaccination, 25 September 2023 to 16 September 2024) and of the autumn booster of 2024 (16 September to 31 December 2024) were estimated by medical risk group among persons aged 60 years and older using Cox proportional hazards models with calendar time as underlying time scale and vaccination status as time-varying exposure. Models were adjusted for age, sex, region and household socio-economic status. From around age 60 onward, intermediate and high medical risk groups had a markedly higher incidence than younger age groups, increasing with age. Persons in the low medical risk group had a low incidence up to the age of 80. In 2024, incidence was lower than in 2023. For both autumn booster rounds, estimated VE against hospitalisation was moderate at 55-67% in the first 3 months post-vaccination. In the high medical risk group, 2023 VE decreased fast and was no longer significant at 6 months post-vaccination. For both years, estimates of the number of averted hospitalizations and number needed to vaccinate to prevent one hospitalization indicated that significant health benefit can be achieved by vaccinating the intermediate and high medical risk groups aged 60 years and older. Efforts to increase the moderate vaccine uptake among risk groups could potentially prevent a considerable disease- and healthcare burden. Highlights- In 2023 and 2024, incidence of COVID-19 hospitalization was highest among medical risk groups aged 60 years and older, despite vaccination campaigns. - Estimated VE against hospitalisation of the 2023 and 2024 autumn booster campaigns was moderate (55-67%) in the first year-quarter post-vaccination among persons aged 60 years and older. - Estimated VE of the 2023 autumn booster decreased over the year, and faster among persons with a medical risk condition. Data availability precluded estimates of 2024 VE beyond the first 3 months since the start of the campaign. - Despite lower and waning VE, the estimated number needed to vaccinate to prevent one COVID-19 hospitalization was much lower among intermediate and high medical risk groups compared with the low medical risk group.

BackgroundHealth status influences uptake of COVID-19 vaccination, with vaccinated individuals generally being healthier than their unvaccinated counterparts. However, the extent to which this healthy vaccinee effect biases vaccine effectiveness estimates remains unclear. This study investigated how different levels of the healthy vaccinee effect may impact these estimates. MethodsThree national, matched, retrospective cohort studies were conducted on the population of Qatar from February 5, 2020-May 14, 2024, to estimate effectiveness of primary- series and booster vaccinations and of natural infection against infection and reinfection. The studies explored three different scenarios for matching by coexisting conditions, each reflecting a different level of health-status imbalance between vaccinated and unvaccinated individuals. ResultsEstimated effectiveness of primary-series and booster vaccinations against infection and against severe, critical, or fatal COVID-19 showed consistent values across the different matching strategies, despite varying hazard ratios for non-COVID-19 deaths. For example, primary-series effectiveness against severe, critical, or fatal COVID-19 was 96.3% (95% CI: 94.5-97.5) when matching by exact coexisting condition types, 94.2% (95% CI: 92.5-95.6) when matching by number of coexisting conditions, and 94.0% (95% CI: 92.3-95.3) with no matching by coexisting conditions. Similar results were observed when the analysis was stratified by the duration of follow-up and for the subgroup of individuals clinically vulnerable to severe COVID-19. Analogous results were found for effectiveness of natural infection against reinfection and against severe, critical, or fatal COVID-19 upon reinfection. ConclusionThe imbalance in health status between vaccinated and unvaccinated individuals in real-world conditions did not introduce a healthy vaccinee bias into the estimated vaccine effectiveness.