New England Journal of Medicine

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 [≥]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...

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...

To evaluate the impact of sex on acute SARS-CoV-2 infection, 668 participants from the ACTIV-2/A5401 study were followed over a 28-day period. A primary analysis was performed on the 469 participants who had quantifiable viral loads at baseline. Male and female participants had comparable nasal SARS-CoV-2 RNA levels at study entry and throughout follow-up. However, sex-specific differences in viral shedding emerged when stratified by duration of symptoms. In the first three days from symptom ons...

BackgroundCoxsackie B viruses cause acute infections and have been linked to chronic diseases like cardiomyopathies, type 1 diabetes, and celiac disease. Despite their clinical significance, no vaccines exist for coxsackie B virus types. PRV-101, a new candidate vaccine covering five coxsackie B virus types, showed good immunogenicity and tolerability in a phase 1 trial (PROVENT). MethodsWe conducted an extended follow-up of the PROVENT trial to assess the long-term immune response and safety o...

This exploratory analysis of PAX LC, a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial examined whether treatment with nirmatrelvir/ritonavir (NMV/r) versus placebo/ritonavir (PBO/r) in individuals with Long COVID could reveal immune features associated with symptom improvement. Eighty-two participants (n=45 PBO/r; n=37 NMV/r) provided blood samples at baseline (Day 0) and post-treatment (Day 28). Baseline demographic and immunological phenotypes were similar in the ...

BackgroundSeveral Shigella vaccine candidates are in late stages of development, and the design of large Phase 3 trials in target populations is underway. Immunologic catch up by unvaccinated infants to vaccinated infants, which is determined by the trial site-specific force of infection, may modify the vaccine efficacy (VE) estimates observed in such trials. To set expectations and support optimal planning of future Shigella vaccine trials, we aimed to quantify the potential bias of VE estimate...

This study estimated early vaccine effectiveness (VE) of the BNT162b2 LP.8.1-adapted vaccine against emergency department/urgent care (ED/UC) and outpatient visits using a test-negative case-control design. Patients from the US Veterans Affairs Healthcare System with an acute respiratory infection (ARI) who underwent SARS-CoV-2 testing from September 10 - November 30, 2025 were included. VE was estimated using multivariable logistic regression adjusted for patient demographics and clinical chara...

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...

Annual influenza vaccination is the cornerstone for seasonal protection, yet antibody responses are highly variable across individuals and over time. To systematically assess the determinants of this heterogeneity, we compiled 20,449 hemagglutination inhibition and neutralization titers from 4,540 participants enrolled in 14 new vaccine studies we conducted and 50 prior studies that collectively span 2010-2023. Seasonal effects dominated, with pre- and post-vaccination titers declining steadily ...

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, 20...

ObjectivesPeriodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common autoinflammatory disorder of childhood, characterized by recurrent febrile episodes driven by dysregulated innate immune activation. Although genetic susceptibility contributes to disease risk, environmental modifiers remain poorly defined. Vaccinations may induce long-lasting modulation of innate immune responses and influence PFAPA incidence. We aimed to assess whether childhoo...

BackgroundSalmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, continues to pose a major public health challenge in many low- and middle-income countries (LMICs). The World Health Organization recommended typhoid conjugate vaccine (TCV) use in countries with a high burden of disease, and/or high rates of antimicrobial resistance (AMR). Recent introductions of TCVs into national immunisation programmes are expected to substantially reduce this burden. However, the i...

BackgroundInterleukin-6 (IL-6) is a cytokine that plays a key role in systemic hyperinflammation and may mediate the relationship between acute COVID-19 and severe long-term outcomes such as Long COVID or death. IL-6 modulating drugs may reduce patients risk of severe post-COVID-19 outcomes. MethodsWe conducted an emulated target trial in a retrospective cohort of patients with moderate-to-severe rheumatoid arthritis who were prescribed IL-6 receptor antagonists (sarilumab or tocilizumab, poole...

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 Controlle...

BACKGROUNDUnderstanding SARS-CoV-2 antibody dynamics is critical for pandemic preparedness, particularly where population immunity has developed through high infection rates with minimal vaccination. Whether predominantly asymptomatic infections confer protective immunity and which biomarkers best predict protection in resource-limited settings remain unclear. METHODSWe conducted a household cohort study in The Gambia over 15 months (March 2021-June 2022) during Delta and Omicron waves, with we...

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 ...

BackgroundSerotype 3 (S3) has remained a major cause of invasive pneumococcal disease (IPD) despite its inclusion in 13-valent pneumococcal conjugate vaccine (PCV). In October 2023, a 15-valent PCV (PCV15) including S3 was introduced into the Catalan universal childhood immunization program. MethodsWe conducted a retrospective pre-post surveillance study to compare pediatric IPD incidence in Catalonia during a pre-PCV15 period (October 1, 2022-September 30, 2023) and two post-PCV15 periods (Oct...

ImportanceRecent reports have highlighted an intense influenza activity related to the circulation of the influenza A(H3N2) subclade k variant. There is no data available on the impact of the emergence of H3N2 subclade k on the severity of the 2025-2026 epidemic or on the clinical phenotype of patients requiring admission to the intensive care unit (ICU). ObjectiveTo compare the clinical presentation, hospital mortality and virological characteristics of patients with laboratory-confirmed influ...

SARS-CoV-2 mutations play a key role in viral evolution, in immune escape, and potentially in disease severity. However, the clinical impact of most mutations remains poorly understood, particularly across different variants. A historical observational study was conducted using SARS-CoV-2 whole-genome sequencing data linked to clinical metadata from 175,503 COVID-19 cases in Israel. The dataset was stratified into four variant-specific periods: B.1.1.7, B.1.617.2, BA.1, and BA.2. Logistic regres...

Annual immunisation against both COVID-19 and seasonal influenza is now becoming standard of care, particularly ahead of anticipated winter waves. These vaccines may be co-administered on the same day or sequentially on separate days. Data on immunogenicity and the impact of consecutive vaccinations on spike-specific humoral and cellular immunity in dialysis patients remain limited. In this real-world observational study, SARS-CoV-2-specific immune responses were evaluated in dialysis patients ...