Nicola P. Klein

Background: Meningococcal serogroup B (MenB) vaccine, 4CMenB, has been licensed in the United States (US) since 2015 for individuals aged 10–25 years. This study assessed 4CMenB in US infants when administered concomitantly with pneumococcal vaccine PCV13 and other routine infant vaccines (RIVs). Methods: This phase 3b, observer-blind, placebo-controlled study (NCT03621670) randomized (2:1) healthy US infants to receive either 4CMenB administered concomitantly with PCV13 and other RIVs (N=786; 4CMenB+RIVs group) or placebo with PCV13 and other RIVs (N=409; Placebo+RIVs group) at 2, 4, 6, and 12 months of age. Primary objectives were to demonstrate the sufficiency of immune responses to MenB indicator strains (individually and combined), to demonstrate the non-inferiority of immune responses to PCV13 administered with 4CMenB+RIVs versus PCV13 plus placebo+RIVs, and assess safety. Immune responses to RIVs administered with 4CMenB+PCV13 versus RIVs plus placebo+PCV13 were investigated as secondary objectives. Results: Pre-specified sufficiency criteria post-dose 3 and post-dose 4 were met for each MenB strain except NHBA and the composite response. Percentages of seroprotected participants (human serum bactericidal assay titers ≥lower limit of quantitation) against MenB indicator strains post-dose 4 were 86.1–99.6% in 4CMenB+RIVs group versus 0.0–2.8% in Placebo+RIVs group. The success criterion for achieving immunological non-inferiority of PCV13 was met, and concomitant 4CMenB administration did not adversely affect immune responses to other RIVs. 4CMenB co-administered with PCV13 and RIVs was generally well tolerated, with no safety concerns identified. Conclusions: 4CMenB was well tolerated and immunogenic in US infants, producing no immunological interference when co-administered with other recommended vaccines.

Background: The 2024–2025 influenza season was the most severe in the United States (US) since 2017–2018, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods: Using electronic healthcare encounter data from 7 VISION sites in 8 US states, we evaluated influenza VE against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024 to April 2025 among children aged 6 months–17 years and adults aged ≥18 years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results: Analyses included 108 618 encounters (5764 hospitalizations and 102 854 ED/UC encounters) among children and 309 483 encounters (76 072 hospitalizations and 233 411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6097/35 765) of cases versus 29.4% (21 449/72 853) of controls were vaccinated. Among adults, 28.2% (21 832/77 477) of cases versus 44.2% (102 560/232 006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41%–60%) against influenza-associated hospitalizations and 54% (95% CI: 52%–55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41%–46%) against influenza-associated hospitalizations and 49% (95% CI: 47%–50%) against influenza-associated ED/UC encounters among adults. Conclusions: Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024–2025 influenza season. These findings support influenza vaccination as an important tool to reduce influenza.

Importance: In the US, adjuvanted or higher-dose influenza vaccines are preferentially recommended for annual use among adults aged 65 years or older. Adjuvanted and high-dose influenza vaccines have not been compared in a pragmatic randomized study. Objective: To assess the relative vaccine effectiveness (rVE) of adjuvanted vs high-dose inactivated influenza vaccine against polymerase chain reaction (PCR)–confirmed influenza in older adults at Kaiser Permanente Northern California (KPNC). Design, Setting, and Participants: In this cluster randomized crossover study, during the 2023 to 2024 influenza season, 65 KPNC facilities were cluster randomized such that approximately half of facilities administered adjuvanted and half high-dose influenza vaccine on the first week of the vaccination season (and thereafter every facility crossed over and alternated formulations weekly). Using Cox proportional hazards regression on a calendar time scale, the rVE of adjuvanted vs high-dose vaccine was estimated for each outcome as 1 minus the hazard ratio, adjusted for age, sex, race and ethnicity, comorbidities, and health care utilization. Study participants included all adults 65 years or older who were vaccinated with adjuvanted or high-dose inactivated influenza vaccine during routine care at a KPNC facility between August 17, 2023, and April 16, 2024. Exposures: Adjuvanted or high-dose inactivated influenza vaccine receipt during the 2023 to 2024 influenza season. Individuals were considered vaccinated 14 days after immunization. Main Outcomes and Measures: The primary outcome was PCR-confirmed influenza in any clinical setting. Secondary outcomes were PCR-confirmed influenza with hospitalization or emergency department visits and hospitalization for community-acquired pneumonia. Outcomes were assessed starting October 1, 2023, or 14 days after vaccination, whichever came later. Results: This study included 429 595 individuals from the 2023 to 2024 influenza season (mean [SD] age, 75 [7] years; 236 857 [55.1%] female; 86 287 [20.1%] Asian, 22 910 [5.3%] Black, 53 820 [12.5%] Hispanic, 1123 [0.3%] American Indian or Alaska Native, 2562 [0.6%] Pacific Islander, 252 709 [58.8%] White, 1638 [0.4%] multiracial, and 8546 [2.0%] unknown race), of whom 212 875 (49.6%) received adjuvanted and 216 720 (50.4%) received high-dose influenza vaccine. There were 836 cases of PCR-confirmed influenza (3.9 per 1000 persons) identified after adjuvanted and 867 cases (4.0 per 1000 persons) after high-dose vaccine. The rVE of adjuvanted compared with high-dose influenza vaccine was 1.5% (95% CI, −8.4% to 10.5%) against influenza, 9.1% (95% CI, −4.0% to 20.4%) against influenza with hospitalization or emergency department visits, and 1.0% (95% CI, −11.4% to 12.0%) against hospitalizations for community-acquired pneumonia. Conclusion and Relevance: In the first season of a large, ongoing study in adults 65 years or older, adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza during the 2023 to 2024 influenza season. Consistent with Advisory Committee on Immunization Practices recommendations, these results support the equivalency of adjuvanted and high-dose influenza vaccines for adults 65 years or older. Trial Registration: ClinicalTrials.gov Identifier: NCT06029933

Background: Vaccination during pregnancy to protect infants against respiratory syncytial virus (RSV) disease relies on transplacental transfer of RSV neutralizing antibodies. Observational natural history studies on correlations between RSV-specific antibody levels and infant protection have, however, had variable results. Methods: This observational natural history study characterized RSV-specific neutralizing antibody levels and described infant RSV disease dynamics in South African and United States (US) maternal–infant pairs. Naturally acquired RSV serum neutralizing titers were determined from 726 pregnant individuals and their infants at birth and assessed in relationship to serum neutralizing titers conferred by serum palivizumab protective levels. Results: In the absence of vaccination, we found no correlation between RSV neutralizing titers and infant protection against RSV-associated lower respiratory tract illness. South Africa versus US comparison revealed similar, broad distributions of maternal serum RSV neutralizing titers but lower transplacental transfer rates in South Africa (0.6 [95% confidence interval {CI}, .6–.7]) than the US (1.3 [95% CI, 1.1–1.4]) and high rates of community spread of infant asymptomatic RSV infection in South Africa versus the US. Conclusions: These findings suggest that the effectiveness of maternal immunization against infant RSV relies on immunization shifting natural distribution of maternal RSV neutralizing titers into the protective range for infants, which is supported by efficacy demonstrated with RSV maternal immunization.

Background: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within US urgent care and emergency department settings. Methods: A retrospective cross-sectional study was conducted for encounters from 4 large, integrated health systems participating in the VIrtual Sars-cov-2, Influenza, and Other respiratory viruses Network (VISION) of adult patients presenting with acute respiratory illness to urgent care or emergency departments and with positive influenza virus test results during the 2023–2024 influenza season. The analysis was restricted to adult patients at higher risk of influenza complications based on presence of underlying medical conditions, older age, pregnancy, and severe obesity. We calculated proportions and odds of prescribed and dispensed antivirals by demographic and clinical characteristics. Results: A total of 10 700 patient encounters were eligible for analysis. Among encounters with a positive standard molecular influenza test result (n = 5231), 58% (range across sites: 47%–64%) were prescribed antivirals, with 67% of prescribing occurring on the encounter date. Among those prescribed antivirals (n = 3050), 80% (range across sites: 75%–91%) had them dispensed, with 65% of dispensing occurring on the prescription date. Encounters among persons aged ≥65 years had lower odds of same-day prescribing (.57; 95% CI: .42–.78) and lower odds of same-day dispensing (.58; 95% CI: .36–.94) compared with those aged 18–49 years. Conclusions: Gaps in antiviral treatment within urgent care and emergency department settings remain for patients at higher risk of influenza complications, notably among older adults. Strategies to improve earlier initiation of antiviral treatment may help reduce the risk of influenza-associated complications.

Background: Pregnant individuals have been historically excluded from clinical trials. To evaluate the safety of vaccines in pregnant individuals and their infants, more data on expected ranges of background rates of pregnancy-related outcomes of interest are needed. The objective of this real-world observational study was to assess background rates of maternal, pregnancy and neonatal/infant outcomes in pregnant individuals and their infants. Methods: We conducted a retrospective observational cohort study of pregnant individuals and their infants using data from Kaiser Permanente Northern California from January 1, 2007, to December 31, 2018. We assessed the incidence proportions of 17 maternal, 4 pregnancy and 10 neonatal/infant outcomes of interest, including eclampsia, preterm labor and stillbirths. Incidence proportions were stratified by maternal age group, race/ethnicity and insurance type. Results: There were 415,074 singleton pregnancies and 413,488 singleton live births included in the study. The most common adverse outcomes (>10%) were preterm labor, gestational diabetes, minor congenital anomalies, macrosomia and large for gestational age. The proportions for pregnancy-related hypertension, fetal asphyxia and preeclampsia were also relatively high (between 5% and 7%). Pregnant individuals (and their infants) in the youngest and oldest age groups, and those of Black race, had the highest proportions for nearly all outcomes. Conclusions: Overall, the proportions of the outcomes assessed were generally consistent with previously published literature of pregnant individuals and their infants in the United States (US). The study provides background rates of important maternal, pregnancy and neonatal/infant outcomes in a US population that may inform vaccine clinical trials and vaccine safety studies in pregnant individuals.

Pregnant people face increased risk of severe COVID-19. Current guidelines recommend updated COVID-19 vaccination (2023–2024) for those aged ≥6 months, irrespective of pregnancy status. To refine recommendations for pregnant people, further data are needed. Using a test-negative design, we evaluated COVID-19 vaccine effectiveness against medically attended COVID-19 with COVID-19–like illness among pregnant people aged 18 to 45 years during June 2022 to August 2023. When doses were received during pregnancy, vaccine effectiveness was 52% (95% CI, 29%–67%); when received <6 months prior to pregnancy, 28% (95% CI, 11%–42%); and when received ≥6 months prior to pregnancy, 6% (95% CI, −11% to 21%). Pregnant people should stay up-to-date with recommended COVID-19 vaccination.