Vaccine

Context: To ensure healthy resettlement and protect US health security, the Vaccination Program for US-bound Refugees (VPR) offers some recommended vaccines to refugees overseas before resettlement to the United States. The selected vaccines and number of doses vary by country of departure. VPR was found to be cost-saving in 2018 but had since expanded to more sites. Objective: Assess VPR's current costs and impact on post-arrival domestic vaccination needs and costs. Setting and Participants: A model-based analysis of the Federal government costs for VPR and post-arrival (US) vaccination of resettled refugees separated across five regions: Africa, Asia, the Middle East and North Africa/Republic of Turkiye and Middle East, Europe, and the Americas using fiscal year 2024 data. Design: We quantified and compared full vaccination costs for refugees under two scenarios: (1) 'No VPR' and (2) 'VPR'. Refugees would receive no vaccines overseas and be fully vaccinated after US arrival under 'No VPR'. Under 'VPR', refugees receive one or two doses of selected vaccines overseas before completing vaccination schedules after arrival. Main Outcomes: Costs were reported in 2023 US dollars for 'VPR' and 'No VPR' scenarios and further subdivided by grouping countries/sites depending on whether the International Organization for Migration (IOM) provides vaccination services for refugees (IOM sites) versus non-IOM providers (non-IOM sites). Results: 'VPR' resulted in average net cost savings of $147 per person or $14.7 million per 100,000-refugee cohort compared to providing all vaccines after US arrival ('No VPR'). 'VPR' was cost-saving across most regions, except for IOM sites in Europe, where a net cost of $44 per person was observed. Net cost savings per person were highest for IOM sites in Africa ($333). Conclusions: VPR remains a cost-saving strategy, while protecting US-bound refugees' health and US health security by preventing disease outbreaks during resettlement.

Introduction: Recommendations from physicians and peers play a crucial role in promoting vaccination. This study evaluated differences in recommendations to others regarding four vaccines with varying efficacy (seasonal influenza, measles, human papillomavirus [HPV], and coronavirus disease 2019 [COVID-19]) between physicians and the general public and examined the impact of birth-year-based vaccination policy changes on these recommendations. Methods: This cross-sectional study was conducted in February 2026 among 492 physicians and 5,252 members of the general public in Japan. Consistency in recommendations across the four vaccines was assessed using the intraclass correlation coefficient (ICC[3,1]), and group differences were examined using a two-way mixed-design analysis of covariance. Multilevel regression discontinuity analyses were performed to evaluate the effects of birth-year-based vaccination policy. Results: Physicians showed significantly stronger recommendations to others than the general public, and their recommendation patterns generally reflected vaccine efficacy. However, physicians showed lower consistency across vaccine types than the general public (ICC[3,1]), driven primarily by heterogeneity in COVID-19 vaccine recommendations. Regression discontinuity analyses showed that birth-year-based vaccination policy, including routine vaccination opportunities, was significantly associated with recommendations to others for measles and HPV vaccines, independently of perceived benefits and risks. Conclusion: To improve vaccination coverage from a public health perspective, it is important for physicians to provide effective vaccination recommendations to the general public on a broader scale; however, it is also necessary to address the heterogeneity in vaccine-specific recommendation patterns among physicians, as observed for COVID-19. Routine vaccination opportunities may increase vaccination coverage not only through the routine vaccination program itself but also through peer effects among the general public. Vaccination policy may therefore influence vaccination coverage not only in the current generation but also in future generations. Designing vaccination policy should consider its long-term impact on future vaccination coverage as well as herd immunity.

Introduction: A cluster randomized trial (CRT) in Bangladesh found that Vi-tetanus toxoid (Vi-TT) vaccine conferred 85% protection to vaccinees at 18 months of follow-up; however, it failed to confer significant herd protection to non-vaccinees. Methods: In the CRT, children aged 9 months to <16 years from 150 clusters received one dose of either Vi-TT or Japanese encephalitis vaccine. To evaluate whether herd protection was evident, we analyzed two years of follow-up data by quartiles of clusters with ascending levels of Vi-TT coverage. Results: The average vaccine coverage across all clusters was 69% among targeted children and 20% in the entire population. Vi-TT provided 83% (95%CI: 74%,89%) total protection among vaccinees, 12% (95%CI: -17%,34%) indirect protection among non-vaccinees, and 53% (95%CI: 40%,63%) overall protection among entire population, irrespective of vaccine coverage. Significant herd protection (47%; 95%CI: 3%,71%) was observed only in the highest quartile of vaccine coverage in the entire population (range 21.5%-26%). No herd protection was evident among targeted children (<16 years), including the highest coverage quartile (72.1%-78.9%), where protection was -8% (95%CI: -108%,44%). Conclusion: Vaccine herd protection, essential for typhoid conjugate vaccines to achieve high overall protection, was evident only in clusters with higher, albeit still modest, coverage in the entire population. Since even high coverage among children <16 years did not generate significant herd protection, higher vaccine coverage across all age groups, including vaccination of adults, may be necessary for TCVs to confer the combined direct and herd protection required for effective typhoid control.

Objective: To assess the impact of a hybrid RSV immunization strategy on hospitalizations, pediatric intensive care unit (ICU) admissions, outpatient visits, and mortality due to LRTI among infants under one year of age in Bogota. Methods: We conducted an ecological interrupted time-series study using weekly surveillance data from Bogota from EW 1 of 2023 to EW 24 of 2026 (181 weeks). Outcomes included weekly rates of all-cause viral LRTI-related general hospitalizations, pediatric ICU admissions, outpatient visits, and deaths among infants younger than one year. Segmented negative binomial regression models adjusted for secular trends, seasonality using Fourier terms, and autocorrelation were used to estimate changes associated with maternal RSVpreF vaccination and nirsevimab implementation. Counterfactual analyses were performed to estimate cases averted and relative risk reductions. Results: Compared with the same period in 2025, the 2026 LRTI hospitalization rate decreased significantly (rate ratio [RR] 0.66; 95% CI 0.64-0.68), as did pediatric ICU admissions (RR 0.78; 95% CI 0.73-0.85) and outpatient visits (RR 0.78; 95% CI 0.77-0.79). Interrupted time-series analyses identified a significant weekly decline in hospitalization trends following maternal RSVpreF introduction (3.9% per week; p=0.023) and a smaller but significant decline in ICU admissions (-2.8% per week; p=0.039). The cumulative relative reduction in hospitalizations was estimated at 47.1% (95% CI 13.9-70.4), corresponding to 7.605 hospitalizations averted over the post-intervention period (EW 47/2025-EW 24/2026). No statistically significant changes were observed for outpatient visits or mortality. Conclusions: Implementation of a hybrid RSV prevention strategy was associated with a substantial reduction in severe LRTI among infants during the first respiratory season following introduction in Bogota. These findings provide the first real-world population-level evidence from Latin America supporting hybrid RSV immunization as a feasible and potentially cost-effective strategy for reducing severe infant respiratory disease in middle-income settings. Keywords: Respiratory syncytial virus (RSV); Maternal RSV vaccination; Nirsevimab; Hybrid immunization strategy; Population impact; Lower respiratory tract infection (LRTI); Interrupted time series ( ITS); Bogota, Colombia.

Background: Live oral rotavirus vaccines were found to be less effective in low-income countries compared to high-income countries when using the same product and dosing schedule. We investigated whether altering dose timing may improve immune protection using a target trial emulation approach. Methods: We emulated a target trial with clone-censor weighting to compare the effectiveness of the recommended 2-dose rotavirus vaccine schedule with a delayed schedule among children under two years of age in Peru and Brazil. Secondary data from the Malnutrition and Enteric Disease Study (MAL-ED) birth cohort (2009-2014) were analyzed. Children were followed from the date of birth until the earliest occurrence of a rotavirus outcome (infection confirmed by PCR or enzyme immunoassay (EIA) or diarrhea confirmed by EIA), protocol nonadherence, loss to follow-up, or their second birthday. Results: We included 154 children in Brazil and 192 in Peru. At two years of follow-up, the risk ratio (RR) for PCR-confirmed infection, using the recommended schedule as the reference, was 1.00 (95% confidence interval [CI]: 0.73-1.37) in Peru and 0.85 (95% CI: 0.31-1.66) in Brazil. In Peru, the delayed schedule was associated with a higher cumulative risk of EIA-confirmed rotavirus diarrhea (RR at two years: 1.73; 95% CI: 1.02-2.77). Conclusions: Delaying the two-dose rotavirus vaccine schedule did not change the cumulative risk of rotavirus infection, but the delayed schedule was associated with a higher risk of rotavirus diarrhea in Peru, where rotavirus incidence was higher.

Introduction: Anaemia and micronutrient deficiencies are common in low- and middle-income countries, where vaccine-induced immune responses are often suboptimal. However, whether pre-vaccination nutritional status influences pneumococcal vaccine immunogenicity in young children remains poorly characterised. Methods: We examined associations between pneumococcal vaccine responses in 670 Kenyan children enrolled in three vaccine trials: PRISM (PCV10; n=195; NCT01028326), FPCV (fractional- and full-dose PCV10/PCV13; n=306; NCT03489018), and PATH-wSP (whole-cell pneumococcal vaccine; n=169; NCT02543892) and baseline anaemia (FPCV and PATH-wSP) and micronutrient status (iron, folate, zinc, and vitamins A, B12, D, and E). Analyses were performed separately for each trial. Primary outcomes were post-vaccination serotype- or antigen-specific IgG concentrations, opsonophagocytic activity (OPA) titres, and composite IgG or OPA z scores. Results: Vitamin B12 and haemoglobin concentrations were positively associated with composite and serotype- or antigen-specific antibody responses in analyses controlling for age, sex, malnutrition and inflammation. In the PRISM trial, PCV10-induced IgG (serotypes 1 and 6B) and OPA (serotypes 1, 4, 14, and 23F) responses were positively associated with vitamin B12 concentrations. Moderate anaemia was associated with lower IgG responses to serotypes 9V and 14 following full-dose PCV13 vaccination (FPCV) and lower antigen-specific IgG responses following the 1 mg PATH-wSP vaccine. No consistent associations were observed for ferritin, folate, zinc, or vitamins A, D, and E. Conclusion: Vitamin B12 deficiency and anaemia were associated with reduced pneumococcal vaccine responses in young Kenyan children. Optimising nutritional status before vaccination could be a strategy to improve vaccine responses in populations where anaemia and micronutrient deficiencies are common.

We compared the immunogenicity of three licensed egg-based inactivated influenza vaccines, including TetrAnflu (Sinovac quadrivalent), Fluarix Tetra (GSK quadrivalent), and Vaxigrip (Sanofi trivalent), in adult healthcare workers in Hong Kong during the 2025/26 season. Paired pre- and post-vaccination sera from age- and sex-matched recipients (n=30 to 40 per group) were tested by hemagglutination-inhibition assays against vaccine strains. After adjustment for age, sex, and sampling interval, the vaccines induced broadly comparable rises in antibody titers, proportions achieving titers >=40, and seroconversion rates, with a superior response to A(H1N1) after TetrAnflu. These real-world findings support the interchangeability of these vaccines for influenza vaccination programs.

During the 2025-26 respiratory virus season, changes to COVID-19 vaccine eligibility, recommendations, and communication may have made vaccination follow-through especially challenging. Under-vaccination may reflect not only lack of willingness, but also breakdowns between willingness and uptake. We analyzed data from 3,390 adults in the CHASING COVID Cohort who completed assessments in August 2025 and March 2026 to examine gaps between vaccine willingness and subsequent influenza and COVID-19 vaccination. Vaccine willingness was defined using prior-season vaccination and stated intention to vaccinate during the 2025-26 respiratory virus season. In August 2025, 73% of participants were influenza vaccine willing and 68% were COVID-19 vaccine willing. Among vaccine-willing participants, 17% and 39% were unvaccinated for influenza and COVID-19, respectively, by March 2026. Absence of prior-season vaccination was the strongest predictor of not vaccinating for influenza and COVID-19, respectively (aRR [95% CI]: 4.04 [3.44-4.74]; 3.01 [2.72-3.34]). Non-vaccination was also associated with food insecurity (1.99 [1.66-2.37]; 1.47 [1.33-1.63]), any healthcare barrier (1.89 [1.57-2.28]; 1.51 [1.36-1.67]), and being not at all confident in vaccine safety (2.95 [2.15-4.05]; 2.21 [1.88-2.59]). Trajectory analyses suggested willingness-uptake gaps reflected incomplete follow-through on intentions and discontinuation among some prior vaccinators. Commonly reported reasons among vaccine-willing non-vaccinators included difficulty finding a convenient time, place, or appointment and, for COVID-19, lack of healthcare provider recommendation. Findings among non-vaccinated adults with prior or stated openness to vaccinate highlight missed opportunities and suggest avenues to improve coverage through strategies that reinforce vaccine confidence, reduce access and logistical barriers, and make vaccination easier to complete.

Background. The Immunization Agenda 2030 (IA2030) tracks new and underused vaccine introduction as an access metric, and its mid-term review calls for stronger country ownership, prioritisation, data use and tailored support in conflict-affected and resource-constrained settings; however, national launch status does not measure recurrent financing, implementation, safety or equity. We examined how recent vaccine-introduction activity was distributed across the WHO African Region. Methods. We conducted a descriptive country-level ecological analysis of all 47 Member States from January 2023 to June 2026. The country was the unit of analysis and contributed one cumulative, unweighted count of nationally endorsed vaccine-introduction and programme-change events. Counts were linked to Gavi eligibility, World Bank FY26 conflict-affected status, broader fragile and conflict-affected situation status in sensitivity analysis, and concurrent system-performance indicators, and modelled with Poisson regression using HC1 robust standard errors. Two Expanded Programme on Immunization (EPI) manager survey waves were summarised at country level. Reporting followed STROBE and RECORD. Results. Seventy-two events were recorded across 38 of 47 Member States: 48 new-antigen introductions, 20 dose or schedule expansions and four combination-vaccine introductions; malaria vaccines accounted for 21. Gavi-eligible conflict-affected countries averaged 2.50 events per country versus 1.27 in both comparison groups. Gavi-eligible conflict-affected status was associated with a higher count (incidence rate ratio [IRR] 1.97, 95% confidence interval [CI] 1.38-2.81; p<0.001), whereas non-Gavi status was not (IRR 1.00, 95% CI 0.54-1.87). The association was strongest for new-antigen introductions (IRR 2.36, 95% CI 1.43-3.91), attenuated but persisted after excluding malaria-vaccine events (IRR 1.77, 95% CI 1.06-2.97), and was robust to baseline introduction-opportunity adjustment (IRR 2.00). Surveys reported constraints in prioritisation, financing, 2026 preparation and post-introduction evaluation. Conclusions. Recent vaccine-introduction activity concentrated where Gavi eligibility, conflict-affected status and weaker concurrent system performance intersected. The association attenuated after excluding malaria-vaccine events, suggesting that the observed financing-conflict gradient was not solely driven by malaria vaccine rollout. However, the ecological design supports no causal inference. Monitoring should pair launch status with financing, implementation, safety and equity indicators to distinguish policy adoption from sustained protection.

Background. Evidence of the effectiveness and cost-effectiveness of new vaccines that reduce the burden of respiratory syncytial virus (RSV) in older populations is emerging. The reported cost-effectiveness of these vaccination strategies varies substantially across different settings. This study assessed the cost-effectiveness of older adult-targeted RSV vaccination strategies in the Australian context and compared findings with published evaluations. Methods. We developed an individual-based dynamic transmission model of RSV infection, linked to a clinical pathways and cost-effectiveness model. We modelled different adult vaccination strategies for the general population and the Indigenous population, and present incremental cost-effectiveness ratios (ICERs) as cost per quality-adjusted life year gained, from a healthcare system perspective. Deterministic and probabilistic sensitivity analyses explored drivers of cost-effectiveness and sensitivity of findings to uncertainty in parameter estimates. Results. Vaccinating the general population of older adults in Australia was not found to be cost-effective at a dose price of 100 AUD, but was found to be cost-saving for Indigenous adults, given the higher disease burden in this population. Individual drivers of ICERs in our setting were dose price, hospitalisation incidence and mortality, however conclusions about cost-effectiveness were robust to joint parameter uncertainty. Conclusions. The cost-effectiveness of vaccinating adults against RSV depends on many uncertain and context-specific quantities. Strategies that target high risk populations were found to be cost-effective in Australia due to the larger avertable burden.

Introduction Hepatitis E virus (HEV) in pregnancy is associated with high maternal and perinatal morbidity and mortality. The safety and efficacy of the recombinant protein HEV vaccine (HEV239, Hecolin) have been established in non-pregnant adult populations but there is limited information among pregnant women. This trial has two co-primary objectives: 1) to assess pregnancy-related and/or serious safety events among pregnant women between 14 and 34 weeks of gestation receiving two Hecolin doses four weeks apart compared to placebo recipients, and 2) to determine immune non-inferiority of pregnant recipients of two Hecolin doses four weeks apart compared to non-pregnant women. Methods and Analysis This is a multi-site, randomized, observer-blinded, placebo-controlled vaccine safety and immunogenicity trial in pregnant women and non-pregnant women of reproductive age in Karachi, Pakistan. A total of 2,358 healthy women will be enrolled, including 2,208 pregnant women between 14 and 34 weeks of gestation, who will be randomized in a 1:1 ratio (stratified by gestational age, 14-27 and 28-34 weeks) to receive either Hecolin or a normal saline placebo in two doses administered 1 month apart during pregnancy and a third dose administered postpartum, approximately 5 months after the second dose. A third arm of 150 non-pregnant women aged 16-45 years will receive Hecolin on 0, 1, and 6 months. The co-primary outcomes will be (i) the proportion of pregnancy-related AESIs and SAEs in pregnant participants from the first dose until the end of study follow-up, compared with placebo, and (ii) the geometric mean concentration (GMC) of anti-HEV IgG at four weeks after the second dose, comparing pregnant vaccine recipients with non-pregnant vaccine recipients (non-inferiority margin of 0.67 for the GMC ratio). Immunogenicity will be evaluated in a pre-specified subset of 300 participants receiving Hecolin, including 150 pregnant participants and 150 non-pregnant participants. Secondary outcomes will include maternal, neonatal, and infant safety outcomes, as well as immunogenicity according to the number of Hecolin doses received and the trimester of vaccination. Ethics and Dissemination The trial was approved by the National Bioethics Committee (NBC) of Pakistan (Reference number: 4-87/NBC-910), the institutional Ethics Review Committee (ERC) of the Aga Khan University (Reference number: 8298), and the Institutional Review Board (IRB) of the International Vaccine Institute (IVI) (Reference number: 2022-007). All participants will provide written informed consent in accordance with Good Clinical Practice. The results will be submitted to World Health Organization (WHO) Strategic Advisory Group of Experts in Immunization (SAGE), and disseminated through conference presentations, and peer-reviewed publications.

BACKGROUND Current polio vaccines face challenges including vaccine-derived poliovirus and high-containment manufacturing. We evaluated a recombinant trivalent virus-like particle (VLP)-based poliovirus vaccine (VPV) for safety and immunogenicity in a first-in-human phase 1 trial. METHODS In this randomized, observer-blind, active-controlled trial, 72 healthy adults (18 to 54 years) were assigned (1:1:1:1) to receive a single dose of VPV at low (45:8:25 D-antigen units [DU] + 0.1 mg aluminum phosphate [AP]), medium (45:8:25 DU + 0.3 mg AP), or high (90:12:45 DU + 0.3 mg AP) doses, or conventional inactivated poliovirus vaccine (cIPV). Primary outcomes were safety and tolerability. Secondary outcomes included neutralizing antibody titers through day 180. RESULTS No serious adverse events or Grade 3 reactions were reported. Solicited adverse events were reported in 77.8%, 55.6%, and 72.2% of the low-, medium-, and high-dose VPV groups, respectively, and 66.7% in the cIPV group. By day 29, VPV induced dose-dependent neutralizing antibody responses. For serotypes 1 and 2, the high-dose VPV group achieved geometric mean titers (GMTs) of 73,582 (95% CI, 31,198-173,545) and 110,623 (95% CI, 59,276-206,451), respectively, comparable to cIPV at 45,161 (95% CI, 20,973-97,244) and 112,361 (95% CI, 58,280-216,625). Although serotype 3 GMTs were lower for the high-dose VPV at 18,905 (95% CI, 8737-40,906) than for cIPV at 61,431 (95% CI, 31,123-121,251), 100% of high-dose VPV recipients achieved neutralizing titers [&ge;]1:1024. CONCLUSIONS A single dose of VPV was safe and highly immunogenic, supporting its potential as a next-generation vaccine to advance global polio eradication. (Funded by the Gates Foundation and Tianjin Leading Enterprises Innovative project 23YDLQSY00100; ClinicalTrials.gov number, NCT06101173).

Objectives: To examine changes in seasonal influenza vaccine uptake among clinical risk groups over periods of differing age-based eligibility. Design: Retrospective cohort study. Setting: Individuals in England registered in the Clinical Practice Research Datalink Aurum. Participants: Between 1,239,802 (2019/20) and 1,289,330 (2023/24) individuals aged 40-69 years in clinical risk groups. Interventions: Natural experiment involving temporary expansion of age-based eligibility for influenza vaccination to include 50-64-year-olds from 2020/21 to 2022/23. Main outcome measures: Influenza vaccine uptake from 1st September to 28th February, incidence rate ratio (IRR) of vaccine uptake across consecutive seasons within age groups, and the ratio of IRRs between age groups. Results: Influenza vaccine uptake increased in all age groups in 2020/21 relative to 2019/20. The increase was larger in individuals aged 50-64 years (13.3%; IRR 1.50, 95% CI 1.50-1.51) compared with those aged 40-49 years (8.3%; IRR 1.35, 95% CI 1.34-1.35) and 65-69 years (6.8%; IRR 1.34, 95% CI 1.33-1.35). From 2020/21 to 2022/23, vaccine uptake decreased, with a more pronounced decline among those aged 40-49 years (-5.4%) compared with age-eligible groups (50-64 years: -3.0%; 65-69 years: -3.1%). The reversion of age eligibility in 2023/24 was associated with a larger decrease in uptake among those aged 50-64 years (-9.6% vs 2022/23; IRR 0.79, 95% CI: 0.79-0.79) compared with those aged 40-49 years (-4.9%; IRR 0.87, 95% CI: 0.87-0.88) and 65-69 years (-3.3%; IRR 0.97, 95% CI: 0.96-0.97). Patterns were broadly consistent across clinical risk groups. Conclusions: The COVID-19 pandemic saw a general increase in seasonal influenza vaccine uptake in clinical risk groups. This increase was larger and more sustained in 50-64 year-olds who had also become eligible based on age. Our findings highlight the potential gains in vaccine coverage among clinical risk groups based on expanded age-based eligibility.

Evidence on vaccine effectiveness (VE) of 2025-26 COVID-19 vaccines is limited. We estimated VE of BNT162b2 LP.8.1-adapted vaccine among non-immunocompromised adults [&ge;]65 years through December 2025 using linked claims and immunization registry data from two U.S. states. VE against COVID-19-related ED/UC encounters was 48% (95% CI:19, 66).

Background Shigella remains an important cause of childhood diarrhoeal disease and a growing contributor to antimicrobial resistance in low- and middle-income countries (LMICs). Several Shigella vaccines are in development, yet little is known about community and stakeholder perspectives regarding the introduction of future Shigella vaccines in Pakistan. We explored perceptions related to diarrhoeal disease, vaccine acceptance, and health system readiness to inform the future introduction of a Shigella vaccine. Methods We conducted a qualitative study in Karachi, Pakistan, between August 2024 and March 2025. Data collection comprised six focus group discussions (FGDs) with caregivers of children under five years of age, and 16 in-depth interviews (IDIs) with key stakeholders including healthcare providers, Expanded Programme on Immunization (EPI) officials, policymakers, technical experts, school administrators, and community and religious leaders. Semi-structured interview guides informed by the Health Belief Model. Audio-recorded interviews were transcribed verbatim, translated into English, and analyzed thematically using both deductive approaches and inductive approaches. Results Four interconnected themes emerged from the data: perceptions of diarrhoeal disease and Shigella; factors shaping acceptance of a future Shigella vaccine; evidence and health-system readiness for vaccine introduction; and vaccine attributes, adoption, and sustainability. Although childhood diarrhoeal disease was widely recognized, awareness of Shigella as a specific pathogen was limited. Participants expressed conditional acceptance of a future Shigella vaccine, influenced by trust, perceived safety, and recommendations from healthcare providers and community leaders. Stakeholders emphasized the need for stronger local evidence on disease burden and cost-effectiveness to support vaccine prioritization, while identifying Pakistan's existing immunization infrastructure as a strength for implementation. Some participants favoured combination vaccines to reduce injections and simplify vaccine delivery, while others emphasized that vaccination should complement continued improvements in water, sanitation, and hygiene. Conclusion Knowledge of Shigella and its vaccine was limited, but stakeholders supported future vaccine introduction if informed by local evidence, policy commitment, and program integration.

The Africa CDC's New Public Health Order aims to improve health, regional self-reliance, and health security by boosting local vaccine manufacturing capacity from <1% in 2022 to 60% by 2040. Although multiple studies have examined vaccine manufacturing capacity in Africa, none quantified future vaccine manufacturing capacity requirements and complexities in capacity planning. We fill this gap by integrating a deterministic approach and discrete event simulation (DES) to estimate vaccine manufacturing capacity requirements and assess the impact of process variability and uncertainty on manufacturing capacity needs. A total of 51 experts were interviewed to design vaccine-specific supply chain networks, collect, and validate data on process-specific parameters. Our findings reveal that deterministic approach provides optimistic capacity estimates but realistic estimates of capacity requirements is possible using DES as it captures variability and uncertainty inherent in vaccine manufacturing. Further evidence shows that reduction in batch yield at any manufacturing stage significantly reduces throughput, while the impact of high batch deviations is vaccine specific and dependent on the manufacturing stage. For multi-antigen vaccines, capacity estimation is complicated by the amplification of process variability, and synchronization of batch arrival and volume. Finally, we estimated that 11 vaccine manufacturing facilities staffed by approximately 8,599 fulltime employees, of whom 43% are technical personnel, would be required to achieve Africa's 2040 ambition. Overall, adopting a system-level perspective, maintaining a high, reliable, and sustainable manufacturing process yield and quality, are important when establishing new vaccine manufacturing facilities.

Introduction Respiratory syncytial virus (RSV) is an important cause of respiratory disease in older adults and adults with chronic medical conditions, contributing substantially to the healthcare burden in Italy. The availability of effective RSV vaccines provides an opportunity to reduce RSV-related morbidity, mortality, and healthcare costs in populations at high risk of severe disease. This study evaluates the potential public health impact and cost-effectiveness of vaccination using mRNA-1345 administered as a single dose compared with no vaccination in Italian high-risk adults aged 60-74 years and all adults aged [&ge;]75 years. Methods A static decision-analytic model was developed to project clinical and economic outcomes over a 5-year time horizon. Economic outcomes were evaluated from the Italian National Health Service (Servizio Sanitario Nazionale, SSN) perspective. Model inputs were informed by the most recent Italian epidemiological, clinical, and economic evidence, supplemented by published international data when necessary. Deterministic, probabilistic, and scenario analyses were conducted to assess the impact of uncertainty in model inputs and assumptions on the study results. Results Vaccination with mRNA-1345 in high-risk adults aged 60-74 years and all adults aged [&ge;]75 years was projected to avert over 19,800 hospitalizations, 4,000 emergency department visits, 381,000 outpatient visits, 6,000 RSV-attributable deaths, and 212,000 antibiotic prescriptions compared with no vaccination over a 5-year period. The total incremental cost of {euro}1,143 million and the additional 47,477 QALYs gained resulted in an ICER of {euro}24,078, which was below the commonly referenced willingness to-pay range of {euro}33,000-40,000 per QALY gained. Sensitivity analyses confirmed robustness of the analysis results. Conclusions Vaccination with mRNA-1345 is a cost-effective strategy for the prevention of RSV in high-risk adults aged 60-74 years and all adults [&ge;]75 years in Italy and has the potential to provide substantial public health benefits.

Background Personal choice in health behaviours raises difficult questions: when individuals freely decline effective preventive interventions, who should bear the resulting costs? This tension is acute in insurance systems where resources are pooled, yet all health systems pursuing Universal Health Coverage must navigate the boundary between collective solidarity and individual accountability. During the COVID-19 pandemic, vaccines were freely available to members of South African private medical schemes, creating conditions in which non-vaccination could plausibly be examined as a matter of personal choice rather than constrained access. This study applied a luck egalitarian framework to assess whether non-vaccination reflected personal choice or constrained circumstance, and to quantify resulting excess costs. Methods A contextual review assessed barriers to vaccination. Using de-identified claims data for approximately 550,000 individuals (March 2020 to December 2022), logistic regression estimated each person's predicted probability of vaccination based on demographic and clinical factors, with observed and predicted rates compared across strata to infer choice versus circumstance. A zero-inflated negative binomial model estimated predicted expenditure among vaccinated members, applied to the full population to simulate universal vaccination. Excess costs were calculated across predicted probability strata. Results Predicted and observed vaccination rates were closely aligned, suggesting that residual non-vaccination in higher-probability groups reflected personal choice rather than constrained circumstance. Observed costs exceeded predicted costs by 22% under universal vaccination, concentrated among older adults and those with comorbidities. Among those with a 60 to 70% predicted probability of vaccination, observed costs exceeded predicted costs by 127.6%. In contrast, among younger, low-risk members, predicted costs slightly exceeded observed expenditure, as vaccination costs were not offset by reduced hospitalisation. Conclusion Risk pooling depends on solidarity, yet non-vaccination due to personal choice shifts costs in ways that challenge fairness in community-rated insurance. These findings highlight the need for transparent deliberation about when personal responsibility should inform equitable health financing design.

Introduction. By the end of 2023, many low-income countries had not reached 50% COVID-19 vaccine coverage, while most high-income countries had exceeded 80%. It remains unclear whether receiving vaccine deliveries translated into faster population coverage. We examined cross-national inequalities in the timing of the vaccine rollout and whether deliveries through the COVID-19 Vaccines Global Access (COVAX) facility were associated with subsequent national uptake. Methods. We conducted an observational study of 218 countries and territories using country-level data up to December 2023. We used generalized additive mixed models to identify country-level correlates of coverage at an early and a later stage of the pandemic, survival analysis to compare the time to 50% coverage between COVAX Advance Market Commitment (AMC) and non-AMC countries, and an event study to estimate the association between the timing of the first COVAX delivery and subsequent monthly coverage in AMC countries. Results. AMC-supported countries reached 50% coverage substantially more slowly than non-AMC countries. The hazard of reaching the threshold was 0.17 times that of non-AMC countries at month 1 (95% CI 0.07 to 0.41) and 0.53 times at month 18 (95% CI 0.33 to 0.85). One year after rollout began, 65.9% of AMC countries (95% CI 56.7 to 76.6) had not reached 50% coverage, compared with 21.1% of non-AMC countries (95% CI 15.1 to 29.5). The timing of COVAX deliveries was not significantly associated with subsequent national uptake in any post-delivery month. In the early stage of rollout, higher maternal mortality was associated with lower coverage, while a larger urban population was associated with higher coverage. By the end of the observation period, larger household size was associated with lower coverage, while higher health expenditure and a larger urban population were associated with higher coverage. Conclusion. Receiving COVAX deliveries was not, on its own, associated with faster coverage. Coverage differences were more consistently associated with country-level structural and health-system characteristics, while we found no significant association with the timing of the first COVAX delivery. Achieving vaccine equality likely requires strengthening the capacity of health systems to convert deliveries into administered doses, and preparedness efforts should invest in last-mile delivery capacity ahead of future emergencies.

Background & aims of study: Current measles outbreaks around the world have highlighted the evolving immunity landscape of some vaccine-preventable diseases (VPDs). In Canada, there have been approximately 1,100 reported measles cases between January and June 2026 alone. This far exceeds the previous average annual case count of <200. This significant outbreak has underscored the need to better understand the present state of population immunity to measles in Canada, an essential input parameter for outbreak response models. Most population immunity in this setting is derived from routine childhood vaccination, but vaccine coverage data is available heterogeneously across the country and is typically collected cross-sectionally to monitor population adherence to immunization schedules rather than to inform population-level susceptibility. This study developed statistical methods to adapt available measles vaccine coverage estimates into more complete estimates of present-day immunity in Canada by age and province/territory (PT). Methods & results: First, a standardized dataset for vaccine coverage by PT was curated from existing publicly-available datasets and reports. A significant number of vaccine coverage estimates were missing by PT, dose, and year. We used Gaussian Process models to impute current coverage with at least one dose of a measles vaccine, to create a complete "modelled dataset" by PT and age. Our modelling framework was also tested against data for England, which was much more complete, to gauge model accuracy. Implications: We developed methodology for estimating vaccine coverage in the absence of detailed population immunity data, to support ongoing measles outbreak modelling response work. While this project focused on measles, we built the associated code/tools such that the methodology can be applied to other vaccine-preventable diseases in future outbreak settings.