Vaccine

Background and Objectives: Influenza vaccination has a strong safety record and is effective in reducing pediatric influenza-associated morbidity and mortality. However, pediatric vaccination coverage (VC) has declined since the 2019/20 influenza season in the United States. We estimated the impact of increased vaccine protection (through increased VC and/or vaccine effectiveness [VE]) on pediatric influenza-associated burden during the 2022/23-2024/25 seasons. Methods: We used a compartmental model and laboratory-confirmed influenza-associated hospitalization, VC, and VE data among children 6 months-17 years to estimate influenza burden from 2022/23-2024/25 (the 'baseline' scenario) and the impact of vaccination. We simulated scenarios that (1) increased VC by five percentage points; (2) increased VE by five percentage points; (3) increased VC and VE by five percentage points; and (4) increased VC to levels achieved in 2019/20 (the season with the highest pediatric VC to date). We estimated the difference in hospitalizations and deaths between each scenario and the baseline scenario. Results: Among children 6 months-17 years, an estimated 120,000 influenza-associated hospitalizations and 1,650 deaths occurred across all seasons at baseline. Increasing VC to 2019/20 levels had the greatest estimated impact, reducing hospitalizations by 8,670 (7.2%) and deaths by 130 (7.9%). Increasing both VC and VE by five percentage points reduced hospitalizations by 6.6% and deaths by 6.7%, whereas increasing VC or VE by five percentage points reduced hospitalizations by 3.1% and deaths by 3.2%. Conclusions: Increasing pediatric influenza vaccination coverage back to 2019/20 levels was estimated to significantly reduce pediatric influenza-associated morbidity and mortality.

Objective: This study estimated the vaccine effectiveness (VE) of 20-valent pneumococcal conjugate vaccine (PCV20) against culture-confirmed pneumococcal pneumonia hospitalizations among adults using a test-negative case-control design. Methods: We included adults ([≥]18 years) hospitalized with pneumonia in the U.S. Veterans Affairs Healthcare System between January 2023 and December 2025 who had respiratory cultures collected. VE was estimated using multivariable logistic regression adjusted for demographic and clinical characteristics. Subgroup analyses were conducted by age, risk group, and U.S. census region. Sensitivity analyses included inverse probability of treatment weighting (IPTW) and evaluation allowing previous PCV13 vaccination. Results: Among 34,009 pneumonia hospitalizations, 837 (2.5%) were Streptococcus pneumoniae culture-positive and 7,428 (21.8%) individuals had received PCV20. PCV20 vaccination was associated with lower odds of culture-confirmed pneumococcal pneumonia hospitalization among adults aged [≥]65 years (VE 20.4%; 95% CI: 2.1%, 35.3%), with greater effectiveness observed among those with chronic medical conditions (VE 24.4%; 95% CI: 0.7%, 42.4%). VE was highest in the Western region among adults aged [≥]65 years (39.6%; 95% CI: 3.2%, 62.3%), a region with a high burden of serotype 4 disease. Overall, VE among adults aged [≥]18 years was 8.8% (95% CI: -8.8%, 23.6%). Findings were consistent across multivariable and IPTW-adjusted analyses. Conclusion: PCV20 provided significant protection against pneumococcal pneumonia hospitalizations among older adults, with greater effectiveness in regions where vaccine-covered serotypes are more prevalent. These findings support the importance of aligning pneumococcal vaccination strategies with regional serotype distribution to maximize vaccine impact.

Background: Recombinant (RIV) and cell culture-based inactivated (ccIIV) influenza vaccines could improve seasonal influenza prevention; however, evidence is limited in how protection may differ among non-egg-based vaccines. Methods: We conducted a randomized trial of RIV versus ccIIV to compare vaccine immunogenicity in adults aged 18 to 64 years during the 2024-25 influenza season (ClinicalTrials.gov, NCT06518577). Active surveillance for influenza-like illness was conducted for six months post-vaccination and cumulative incidence of influenza by vaccine type was compared to estimate relative vaccine efficacy. Participants were tested for influenza by reverse-transcription polymerase chain reaction or rapid antigen tests. Immunogenicity was evaluated by hemagglutination inhibition (HAI), virus microneutralization (MN), and neuraminidase inhibition (NAI) assays in a subset of blood specimens collected pre-vaccination and one-month post-vaccination. Results: Among the 591 participants, 25 cases of influenza A were detected; 2.4% cumulative incidence among RIV recipients versus 6.1% among ccIIV recipients. The probability of influenza was 61% lower with RIV than ccIIV (95% confidence interval: 7 to 84). Among 151 participants, post-vaccination HAI and MN titers vaccine components were higher among RIV recipients while NAI titers were higher among ccIIV recipients. Conclusions: RIV provided better protection than ccIIV against influenza A illness in adults during the U.S. 2024-2025 season.

There is currently no clinical data for the effectiveness of the only licensed Ebola virus disease vaccine (Ervebo) against Bundibugyo virus disease. A number of studies have shown immune cross-reactivity with Bundibugyo virus after Ervebo vaccination. However, antibody recognition of Bundibugyo is around 2.8-fold lower than recognition of Ebola virus. Here, we aimed to infer how a 2.8-fold drop in immune recognition may affect Ervebo protection against Bundibugyo virus disease based on analysis of data on Ervebo immunogenicity and protection from Ebola virus disease. This work has three main components. Firstly, we analysed the timing of vaccine protection in the Ervebo pivotal ring vaccination clinical trial. Secondly, we performed a systematic review and meta-analysis of antibody responses to Ebola virus after Ervebo vaccination over time. Thirdly, we combined these data with previously reported data on the cross-reactivity to Bundibugyo virus to infer protection of Ervebo against Bundibugyo virus disease. We find that the clinical trial data for Ervebo supports vaccine protection beginning earlier than 10 days after vaccination. Secondly, binding antibody levels against Ebola virus on day 28 post vaccination (peak responses) were on average 12.9-fold (95% confidence interval, CI: 6.4 - 26.0) higher than on day 7, 6.3-fold (95% CI: 3.7 -10.8) higher than on day 10, and 2.5-fold (95% CI: 1.4 - 4.4) higher than on day 14 (neutralising antibodies showed similar results). Finally, we consider the scenarios where antibody levels to Ebola virus at day 7 or 10 are putative protective thresholds against Ebola virus disease, and we assume these thresholds also apply for Bundibugyo virus disease. Then, with a 2.8-fold reduction of responses to Bundibugyo compared to Ebola virus, we predict antibody responses to Bundibugyo virus after Ervebo vaccination are likely above these putative protective thresholds.

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.

BackgroundSince the COVID-19 pandemic, parental delays and refusals of well-established, safe, and effective childhood vaccinations have contributed to the resurgence of infectious diseases. This raises concerns that COVID-19 vaccine hesitancy may also extend to novel vaccines for children when introduced in the future. This study examined caregivers, who included healthcare workers (HCWs), perceptions of novel vaccinations for children ages 0-17 years old and intentions to vaccinate children and adolescents ages 12-17 years against COVID-19. MethodsWe conducted a secondary data analysis of a larger cross-sectional survey administered to parents/caregivers of children ages 0-17 years in Lusaka, Zambia, between 13 November and 15 December 2023. Vaccination intention for COVID-19 was specifically focused on caregivers of adolescents ages 12-17 years, following COVID-19 vaccination guidelines during the study. Descriptive statistics were used to explore demographic characteristics, vaccination history, and caregivers COVID-19 vaccination status, along with their childrens routine childhood vaccine histories and perceptions of COVID-19 and novel vaccinations. ResultsAmong 277 caregivers (66.8% women, median age: 35 years), 93.1% reported that their child had received all recommended routine childhood vaccinations. COVID-19 vaccine uptake was higher among HCWs (68.2% with [≥]2 doses) than among community members (40.8%) and having [≥]2 doses was associated with higher COVID-19 vaccine uptake among their adolescents ages 12-17 years. 58.0% of caregivers indicated that their 12-17 years old adolescents had received at least one COVID-19 vaccine dose. Overall intention to further vaccinate children against COVID-19, especially among those already unvaccinated, remained low, with 24.7% of caregivers reporting no intent to vaccinate their children. Protection from hospitalization and death from malaria, TB, HIV, pneumonia, influenza, and diarrheal diseases were the most cited reason (79.1%) for intention to vaccinate children with novel vaccines for these diseases. The most prominent reasons for reluctance towards future vaccines were the fear of potential side effects (45.5%) and insufficient knowledge about vaccination benefits and risks (31.8%). Caregivers most trusted the Ministry of Health (86.6%) and healthcare professionals (66.8%) as sources of vaccine information. ConclusionsWhile routine childhood vaccine uptake remained high, acceptance of COVID-19 and future novel vaccines for children was lower and was influenced by caregivers own vaccination status. Targeted and transparent communication through trusted sources such as the Ministry of Health and healthcare professionals may be critical for addressing safety concerns and strengthening confidence in novel childhood vaccines.

Background: Pseudomonas aeruginosa is a major opportunistic Gram-negative pathogen responsible for healthcare-associated infections, while increasing antimicrobial resistance has narrowed therapeutic options. Vaccine development therefore represents an important complementary strategy for prevention. This study compared the immunogenicity and protective efficacy of a formaldehyde-inactivated whole-cell vaccine with a sonicated whole cell extract preparation against multidrug-resistant (MDR) P. aeruginosa in mouse model. Methods: Clinical P. aeruginosa isolates were obtained from specimens collected at Dhaka Medical College Hospital between July 2022 and February 2026. Formaldehyde-inactivated whole-cell and sonicated whole cell extract preparations were produced from P. aeruginosa. A total of 144 female Swiss albino mice aged 6-8 weeks were used: 120 mice were allocated to two independent immunization experiments and 24 mice were used for LD50 determination. Mice received three intramuscular immunizations on days 0, 14, and 28. Antigen-specific serum IgG was assessed by enzyme-linked immunosorbent assay (ELISA), functional antibody activity was evaluated by serum bactericidal assay (SBA), and protective efficacy was assessed following lethal intraperitoneal challenge. Results: Ten isolates from MDR P. aeruginosa were selected by simple random sampling from the clinical isolates for vaccine preparation. The estimated protein concentration of the sonicated preparation was 1.872 mg/mL. Both vaccine groups developed significantly higher anti-P. aeruginosa IgG responses than the control group after immunization (p<0.001). Following lethal challenge, survival was 100% in mice receiving the formaldehyde-inactivated vaccine and 91.7% among mice receiving the sonicated preparation; no control mice survived. Between-vaccine differences in survival were not statistically significant. SBA demonstrated complement-dependent bactericidal activity in sera from both vaccinated groups, with activity detectable to a dilution of 1:32 for the whole-cell vaccine and 1:64 for the sonicated preparation. Conclusions: Both vaccine preparations elicited strong humoral responses and substantial protection against lethal MDR P. aeruginosa challenge in mice. The findings support further investigation of multicomponent P. aeruginosa vaccine strategies, although additional studies using multiple challenge strains and broader immunological endpoints are required before conclusions regarding translational efficacy can be drawn.

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.

Introduction: Despite a significant increase in influenza burden in Brazil in 2025, the associated vaccine effectiveness has not included the key end-of-winter period. Methods: The number of trivalent influenza vaccine doses received within a calendar year was the key exposure. In-hospital mortality and length of stay, use of the intensive care unit (ICU), and ICU stay were outcome measures. Secondary data from January 2003 to October 2025 were retrieved and analysed by Poisson regression. Results: Influenza vaccine uptake among SARI-hospitalised patients dropped from about 70% in 2023 to a 40-50% level in 2024 and 2025. A single vaccine dose reduced outcomes by 10-13% compared to unvaccinated patients. Two doses per year significantly reduced mortality (32%), ICU admissions (52%), and ICU stay (28%). Conclusion: Two doses of influenza vaccine were moderately effective in decreasing in-hospital mortality and stay among SARI-hospitalised influenza patients. Including 50-59-year-olds in a priority vaccination group may significantly reduce influenza-related adverse outcomes.

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).

Introduction: This study compared the health and economic impact of the 21-valent pneumococcal conjugate vaccine (aPCV21) vs the 20-valent pneumococcal conjugate vaccine (PCV20) on invasive pneumococcal disease (IPD) and post-meningitis sequelae (PMS) among adults aged 65 years and older in the United Kingdom (UK). Methods: A published Markov model was used to simulate a single-cohort of vaccine-naive adults who became eligible for age-based vaccination at age 65 years, with uptake occurring over time. The cohort was followed until a maximum age of 100 years. Model inputs were derived from publicly available national health data and published reports. Outcomes were discounted at 3.5% annually, and costs were adjusted to the 2024 Great Britain Pound ({pound}). Additional analyses explored the impact of changing the age-based recommendation from 65 years to 75 years. Scenarios involving instantaneous vaccine uptake rates were included as part of the sensitivity analyses. A deterministic sensitivity analysis was performed on the incremental direct medical costs between vaccinating with aPCV21 vs PCV20 under the age-based recommendation of 65 years. Results: Using an age-based recommendation of 65 years, aPCV21 led to fewer cases, deaths, and costs than PCV20. Compared with PCV20, aPCV21 averted an additional 138 IPD cases, 1 PMS case, and 22 IPD deaths, saving {pound}1.2 million in direct medical costs. Raising the age-based recommendation from 65 to 75 years and using aPCV21 (or PCV20, respectively), resulted in 120 (92) additional IPD cases, 2 (1) additional PMS case(s), 19 (14) additional IPD death(s), and an extra {pound}1.1 ({pound}0.8) million in direct medical costs. The deterministic sensitivity analysis showed that aPCV21 reduced direct medical costs across all parameter ranges. Conclusions: Compared with PCV20, aPCV21 prevented more IPD cases, IPD deaths, and direct medical costs among older adults in the UK. Changing the age-based recommendation from age 65 to 75 resulted in worse health and economic outcomes. Key words. Pneumococcal infections; pneumococcal vaccines; vaccines, conjugate; serotype; United Kingdom; health costs

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.

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.

There are currently no approved vaccines or medical countermeasures for use in prevention or treatment of Bundibugyo virus disease. A critical question is whether the existing vaccines approved for use against Ebola virus disease could provide sufficient cross-reactivity and cross-protection against Bundibugyo virus disease. We performed a systematic review and meta-analysis of published studies of antibody cross-reactivity to Bundibugyo virus (BDBV) after vaccination with previously approved Ebola vaccines (Ervebo or Zabdeno/Mvabea). We find on average a 2.8-fold (95% predictive interval, PI: 2.6-3.0) drop in binding (n = 8 observations from 4 studies) and 3.1-fold drop (95% PI: 2.0-4.8) in neutralization (n = 2 observations from 1 study) between Ebola virus and BDBV antigens after Ervebo vaccination, which appears maintained over time after vaccination. Very limited data on cross reactivity after Zabdeno/Mvabea vaccination suggests a higher drop in recognition of BDBV (39.7-fold, 95% PI: 24.8-63.8; n = 3 observations from 2 studies). In addition to analysis of antibody recognition in humans, we also investigated evidence for vaccine protection from BDBV challenge in animal models after Ervebo or other recombinant vesicular stomatitis virus (rVSV) based vaccines containing only Ebola antigen. A single study in NHP showed non-significant vaccine protection from BDBV challenge, while a study in ferrets showed significant protection after both one and two doses. The available data demonstrate immune cross-reactivity and some evidence for protection in animals, although further clinical and pre-clinical data is urgently needed to inform decisions on the use of Ervebo to protect against Bundibugyo virus disease.

Background: Waning vaccine protection and variable epidemic timing create a tradeoff between vaccinating before influenza circulation and preserving protection when disease burden is greatest. Existing guidance does not quantify the week that best balances this tradeoff. Objective: To estimate the optimal week for influenza vaccination while accounting for uncertainty in epidemic timing and vaccine protection. Design: Simulation-based probabilistic decision analysis. Setting: United States outpatient influenza surveillance from the 50 states and District of Columbia during the 2010/11 through 2018/19 and 2023/24 through 2025/26 seasons. Participants: People in the United States who would receive 1 influenza vaccine dose. Interventions: Vaccination during Morbidity and Mortality Weekly Report (MMWR) weeks 36 through 12. Measurements: We combined influenza-like illness (ILI) syndromic surveillance and influenza-specific data with uncertainty in epidemic timing, initial vaccine effectiveness, waning, and immune-response lag. For each candidate week, the model estimated direct protection against outpatient surveillance burden. Results: The primary model identified the optimal time to vaccinate as week 47, with weeks 47-48 being of similar utility. Our influenza-weighted outpatient analysis (ILI+) selected week 48. Compared with week 44, near the end of the current September-October guidance window, week 48 reduced modeled influenza-weighted outpatient burden by 50 visit equivalents per 10,000 weekly encounters. Limitations: The model assumed vaccination would occur, used outpatient surveillance burden rather than severe outcomes, and did not incorporate transmission effects. Conclusion: Under the primary waning model, these findings favor vaccinating during weeks 47-48, approximately late November through early December, for most one-dose recipients.

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: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

Importance: Maternal vaccination and long-acting monoclonal antibodies are now available in the U.S. to prevent RSV. Long-acting monoclonal antibody administration in the U.S. commonly occurs after hospital discharge in outpatient settings, leaving some infants unprotected early in life when severe RSV risk is highest. Comparative effectiveness between the two interventions and whether delays affect effectiveness estimates have not been quantified. Objective: To evaluate the effectiveness of infant long-acting monoclonal antibody strategies and a maternal vaccination strategy, each compared to no intervention, and the comparative effectiveness of intervention strategies when accounting for real-world delays in monoclonal antibody receipt. Design: Cohort study using target trial emulation to compare four strategies for prevention of RSV-related outcomes. Setting: The U.S. between 2023 and 2025 using a nationwide database of employer-sponsored commercial insurance claims. Participants: 120,586 commercially insured mother-infants, whose infants were born in the U.S. during the 2023-2024 or 2024-2025 RSV season. Infants who could not be paired with their mother's record, did not enroll in commercial insurance within 75 days from birth, received palivizumab, and had an implausible birth date were excluded. Interventions: Comparison of four RSV prevention strategies: (i) maternal RSVpreF; (ii) long-acting monoclonal antibody given within the first week of life (mAb as intended); (iii) long-acting monoclonal antibody given within a six-month grace period from birth (mAb within grace period); and (iv) a control. Main outcomes and measures: Effectiveness against first RSV-associated hospitalization and medically-attended RSV illness was summarized using adjusted hazard ratios (aHR) and estimated using an inverse propensity weighting approach, with weights accounting for maternal age, maternal comorbidities affecting pregnancy, obstetric and newborn complications, season, region, and birth timing relative to October 1. A weighted Kaplan Meier estimator was used to estimate strategy-specific cumulative incidence of RSV outcomes over time. Results: In the first five weeks of life, the mAb within grace period strategy doubled the hazard of RSV hospitalization (aHR: 2.0 [95% CI: 1.0-4.9]) and increased the hazard of medically-attended RSV (aHR: 1.6 [95% CI: 1.0-2.7]) compared to the maternal RSVpreF strategy. The hazard for RSV hospitalization was similar for the mAb as intended strategy compared to the maternal RSVpreF strategy (aHR = 0.9 [95% CI: 0.3-1.9]). Conclusions and relevance: RSVpreF and monoclonal antibodies were similarly effective when monoclonal antibodies were administered close to birth, but when accounting for real-world delays in monoclonal antibody receipt, the maternal RSVpreF strategy was more effective than the mAb within grace period strategy.

Background/Objectives: Older adults are at high risk of influenza-related severe disease and complications. HD-IIV, currently recommended for adults [&ge;]65 years, is egg-based and may be subject to egg-adapted mutations. An mRNA-based vaccine for influenza, mRNA-1010, has been approved by the Food and Drug Administration. Given the clinical benefits observed in mRNA-1010 clinical trials and potential to avoid egg-adapted mutations, this analysis explores the clinical impact of mRNA-1010 compared to HD-IIV in those [&ge;]65 years in the United States. Methods: This study used a decision-analytic model of influenza infection and downstream outcomes to project influenza burden with each vaccine over a one-year timeframe. Vaccine coverage, HD-IIV vaccine effectiveness (VE) and influenza epidemiology was estimated based upon Centers for Disease Control and Prevention data. The relative VE (rVE) for mRNA-1010 vs. HD-IIV was modelled based on data from the clinical trial and published literature on the impact of egg adaptation. Results: The base-case analysis suggests mRNA-1010 may prevent an additional 232,200 symptomatic influenza infections, 130,000 outpatient cases, 21,100 influenza-related hospitalizations, and 2,200 influenza-related deaths compared to HD-IIV. The number needed to vaccination to prevent one hospitalization was 514 or mRNA-1010 vs no vaccine and 404 for HD-IIV versus no vaccine, for an incremental NNV of 110. Scenario and deterministic sensitivity analyses results indicate that clinical outcomes prevented by mRNA-1010 are most sensitive to influenza incidence and VE. Conclusions: mRNA-1010 may improve protection against influenza in US adults aged [&ge;]65 years, leading to meaningful reductions in the clinical influenza-related disease burden in older adults.