Janet A. Englund

Immunization during pregnancy to protect the woman, fetus, and/or the infant is an important strategy to provide protection to individuals at high risk for infectious complications due to bacteria, viruses, or parasites. This is not a new strategy, as vaccines have been documented to provide protection to mothers and infants for many years against pathogens such as smallpox and tetanus. Despite data showing safety and efficacy, few vaccines have been tested in rigorous clinical trials or been licensed for use in pregnancy. Current vaccines recommended for use in pregnancy include tetanus vaccine, combination vaccines including tetanus-diphtheria-acellular pertussis vaccine, inactivated multivalent influenza vaccines, and bivalent RSV prefusion protein vaccines. Vaccines considered for use in pregnancy must take into account the epidemiology of disease and the target population. Preclinical evaluation, as for other vaccines, is critical prior to clinical studies, which generally first take place in healthy young nonpregnant adults prior to small clinical trials in pregnant persons. Clinical studies leading toward licensure require clear definitions of inclusion and exclusion criteria, safety parameters, and study endpoints. Studies done in lower income countries must also follow these criteria closely, with determination of gestational age an important component of entry into clinical studies. Follow-up of subjects during pregnancy, delivery, and after delivery is required, as well as follow-up of infants born to study subjects for at least 6 months to 1 year following birth. Vaccine efficacy should be determined using readily determined objective criteria that can be used in different socioeconomic settings. Despite potential benefits, challenges remain for the testing, licensure, and uptake of new maternal vaccines.

Background: The relationship between recent viral infection and subsequent susceptibility to, or protection against, other viruses remains unclear, particularly across age groups and symptom status. Methods: A prospective cohort study enrolled participants aged 6 months to 49 years in Washington and Oregon, USA, 2022–2024. Weekly nasal swabs were tested for SARS-CoV-2, respiratory syncytial virus (RSV), and influenza A/B; additional swabs were collected during symptomatic illness and were also tested for parainfluenza (PIV) 1–4, endemic human coronaviruses (hCOV), adenovirus, human metapneumovirus, human rhinovirus (hRV), and enteroviruses. Proportional hazards regression models were used to characterize associations between incident symptomatic infection (illness) and history of recent illness due to other viruses (within 1–7, 8–14, 15–30, 31–60, 61–90, 91–180 days), adjusted for geographic region, age, sex, daycare/school/work attendance, household size, and number of children in the household. For SARS-CoV-2, influenza, and RSV, these analyses were repeated to study incidence of infection (including asymptomatic cases). Findings: Of 3,560 participants, 2,969 (83%) had ≥1 illness over 4,299 person-years. Adjusted hazard ratios (aHRs) in the short term (≤2 weeks) after an illness were predominantly below 1, indicating that recent viral illness was often associated with lower risk of subsequent illness with other viruses. Across age groups, recent hRV illness was associated with lower risk of hCOV, PIV, and RSV illness (aHRs 0.07–0.27). SARS-CoV-2 illness was associated with a higher short-term risk of adenovirus and PIV illness (aHRs 3.20–3.33). In children aged 6 months–4 years, recent influenza illness was associated with higher short-term risk of SARS-CoV-2 illness. Including asymptomatic infections generally attenuated these associations. Interpretation: Some viral illnesses may alter short-term susceptibility to subsequent viral illnesses. Interactions may differ by age and symptom status. Funding: US Centers for Disease Control and Prevention; Washington State Department of Health.

Background: Globally, RSV declined to historically low levels following stay‐at‐home orders in 2020 and re‐emerged as restrictions lifted, with large inter‐seasonal outbreaks and other shifts in epidemiology. The effect of the pandemic restrictions on genomic diversity has not been well studied. Methods: Individuals with respiratory symptoms were enrolled into community‐based surveillance studies and provided nasal swabs over three respiratory virus seasons from 2019 to 2022 in the Seattle metropolitan area in Washington State, USA. Samples were tested for RSV by RT‐qPCR, with whole genome sequencing performed for a subset. Results: Among children and adults, respectively, 1.8% (232/13,014) and 0.2% (86/46,042) of samples tested positive for RSV‐A and 1.1% (139/13016) and 0.3% (119/46043) for RSV‐B. Positive cases were observed in childcare ( n = 39), clinic ( n = 270), university ( n = 20), workplace ( n = 32) or nursing facility ( n = 1) sites and through at‐home self‐administered testing ( n = 253). Median age for all participants was 33 years (IQR: 23, 48) and 3 years (IQR: 3, 33) for those who tested positive. Cough (≥ 85%) and rhinorrhea (≥ 85%) were the most common symptoms for RSV cases. During 2019–2020, six RSV‐A and three RSV‐B lineages circulated (majority lineages A.D .1 and B.D.4.1.1). Almost no RSV was detected during 2020–2021. During 2021–2022, RSV‐B lineage B.D.E.1 was dominant. Conclusions: In a community surveillance study spanning several years, RSV was commonly detected in young children across several sites. Circulation of RSV was disrupted by pandemic mitigation measures, with shifts in genomic diversity detected after lifting of pandemic restrictions.

Human seasonal influenza evolves rapidly, necessitating twice yearly decisions about whether to update the strains in the vaccine. To help inform this decision, we have been using high-throughput sequencing-based neutralization assays to make twice yearly measurements of how recent human sera neutralize current human H3N2 and H1N1 strains. Here we provide the third installment in this series of measurements by reporting 52,268 titers representing neutralization of 148 viral strains by 355 human sera collected between April and August of 2026. Our measurements show that new H3N2 subclade K strains with mutations in antigenic region D and new H1N1 subclade D.3.1.1 strains with mutations in antigenic region Sa (such as G155E) have reduced neutralization by human sera, with notable heterogeneity in the impact of some of these mutations across sera from different individuals. This paper is accompanied by an interactive summary ( https://jbloomlab.github.io/flu-seqneut-2026/summary.html ) that enables detailed exploration of the results, and all titer data are publicly available for further analysis to aid vaccine antigen selection and studies of viral evolution.

Background: Respiratory syncytial virus (RSV) causes substantial morbidity in pediatric hematopoietic cell transplant (HCT) recipients; however, risk factors for severe disease remain incompletely characterized. Methods: We conducted a multicenter retrospective cohort study across 16 U.S. transplant centers, evaluating children and adolescents (0–19 years) who underwent HCT and developed a laboratory-confirmed RSV infection between 2010 and 2019. Clinical characteristics, laboratory values, and immunosuppressive and transplant history were analyzed. Outcomes included new or increased supplemental oxygen requirement, RSV-related hospitalization, progression to lower respiratory tract infection (LRTI), invasive mechanical ventilation, and 90-day mortality. Univariate logistic regression was used to screen candidate predictors, followed by the least absolute shrinkage and selection operator for variable selection, and multivariable logistic regression to identify independent predictors associated with clinical outcomes. Results: Among 204 pediatric HCT recipients with RSV infection, 41.7% had RSV-related hospitalization, 21.2% required new or increased supplemental oxygen, and 4% required invasive mechanical ventilation within 28 days after the diagnosis. Mortality within 90 days was 5.4%, with one death attributable to RSV. In multivariable models, female sex, younger age (particularly <5 years), neutropenia (ANC <500/mm3), presence of co-pathogen in the respiratory tract and chronic lung disease were independently associated with this oxygen outcome, while non-peripheral graft sources and T-cell–depleting therapy were associated with RSV-related hospitalization. Conclusions: Severe outcomes are common in pediatric HCT recipients with RSV infection. Younger age, markers of impaired immune recovery, history of chronic lung disease, and T-cell–depleting therapy are major determinants of adverse outcomes. These findings support targeted risk stratification and may inform preventive and treatment strategies in this high-risk population.

Background: Infants are at risk of severe respiratory syncytial virus (RSV) infection. We characterized the humoral immune response of infants with primary RSV infection. Methods: Term infants hospitalized for RSV acute respiratory infection (ARI) or non-RSV ARI (controls) were enrolled from November 2018 through March 2020 at 5 pediatric medical institutions. Adult controls were women aged 18–45 years without acute RSV infection. Acute and convalescent sera were tested for homologous and heterologous neutralizing antibodies (NtAbs), competitive antibodies (CAs) to sites Ø, II, IV, and I on the fusion (F) glycoprotein, and anti-postF and 27-amino acid peptide (p27) immunoglobulin G (IgG). Geometric mean titer or CA concentrations of acute and convalescent sera were compared between and within groups. Results: Sixty-six infants (49 RSV infected and 17 controls) were enrolled. Median age was 76 (interquartile range [IQR], 45–179) days and 151 (IQR, 72–207) days for the RSV and control groups, respectively. NtAb and CA at hospitalization were low among infant groups. Postinfection, RSV/A induced robust homologous and heterologous NtAb responses while RSV/B caused a robust NtAb response only to RSV/B. RSV/A infection generated significant CA rise to sites IV and II, while RSV/B infection resulted in only site II CA rise. Rises in postF and p27 IgG were not detected. Postinfection RSV antibody levels in infants were markedly lower compared to those in control adult women. Conclusions: RSV-infected infants had low preinfection levels of protective antibodies. Infants infected with RSV/A compared to RSV/B generated a more robust NtAb response, highlighted by a broader CA response to sites II and IV.

Background: Comprehensive data are needed to guide the use and interpretation of molecular respiratory viral testing in evaluating infants 0 to ≤90 days old for invasive bacterial infections (IBIs). We aimed to describe the frequency and severity of respiratory viral infections in febrile and nonfebrile infants 0 to ≤90 days of age with emergency department visits or hospitalizations for acute respiratory illness and to quantify the occurrence of IBI (bacteremia and bacterial meningitis) in these groups. Methods: The New Vaccine Surveillance Network conducts acute respiratory illness surveillance at 7 US pediatric medical institutions in the United States. We conducted a cross-sectional analysis of febrile and nonfebrile infants 0 to ≤90 days of age enrolled in the emergency department or inpatient hospital settings. Respiratory viral detection from research respiratory samples in the context of clinical severity and IBI was examined. Results: Three thousand seven hundred and eighty febrile and nonfebrile infants 0 to ≤90 days of age enrolled from December 1, 2016, to March 31, 2020. Respiratory syncytial virus was the most common virus detected regardless of febrile status. IBIs were significantly more frequent in febrile infants without a respiratory virus compared with those with a respiratory virus detected (4.9% vs. 1.3%; P < 0.001). IBIs were not detected in infants with respiratory syncytial virus (n = 259), parainfluenza virus (n = 66), human metapneumovirus (n = 13), influenza virus (n = 67), or adenovirus (n = 11) alone. IBI and respiratory viral coinfections were found in infants with endemic coronaviruses (5.8%, 3/52), rhinovirus/enterovirus (2.2%, 7/324) and viral coinfections (2.0%, 2/99). Conclusions: These data suggest that febrile infants 0 to ≤90 days old with certain respiratory viruses are at lower risk of IBI.

Background: Households remain high-risk settings for SARS-CoV-2 transmission. Identifying contemporaneous risk factors for infection among household contacts of an index case can guide public health strategies. Methods: We conducted a prospective observational household study in Oregon and Washington, USA, during 2022-2024. Participants completed enrollment, weekly, and follow-up symptom surveys and submitted sera and weekly nasal swabs. Swabs were tested for SARS-CoV-2 by polymerase chain reaction (PCR) ; a subset of positive specimens underwent whole genome sequencing. Sera was tested for SARS-CoV-2 antibodies. We evaluated individual and household-level factors associated with risk of SARS-CoV-2 infection after 1-14 days (likely secondary infection) among household contacts within households with a distinct (ie, single) index case. Results: Overall, we identified 617 households with a distinct index case, of which 46% were children. The estimated secondary infection rate was 16% (95% CI 13.6%, 18.8%), reflecting 203 secondary infections among 1267 household contacts. Among household contacts, factors associated with secondary infection included low anti-nucleocapsid antibody titers (RR: 1.88, 95% CI 1.34, 2.64), or residing with an index case who was symptomatic (RR: 1.85; 95% CI 1.04, 3.23), or had viral detection >1 week (RR: 2.15, 95% CI 1.55, 2.97). Among 136 sequenced index-secondary case pairs, 128 (94%) shared SARS-CoV-2 lineages. Conclusion: During 2022-2024, 1 in 7 household contacts of index cases were infected within two weeks, with higher rates in contacts with lower antibody levels and when index cases had symptoms or longer viral detection. These findings can inform ongoing strategies to mitigate SARS-CoV-2 community transmission.

Few studies have characterized immune correlates of SARS-CoV-2 infection risk in children, particularly those with hybrid immunity from vaccination and prior infection. We conduct a prospective community-based cohort study of 1509 U.S. children (2022–2024), performing weekly SARS-CoV-2 PCR testing and measuring baseline binding and neutralizing antibody titers against multiple variants. Higher antibody levels, notably nucleocapsid-binding and Omicron-specific neutralizing antibodies, are significantly associated with reduced risk of SARS-CoV-2 infection after adjusting for age, recent infection, exposure settings, and temporal trends (adjusted hazard ratios ranging from 0.60 to 0.87 per positive unit difference in log₁₀-fold antibody level (AU/mL)). Secondary analyses suggest these findings are robust to multiple stratifications of SARS-CoV-2 immune status, are relevant across different pediatric age groups, and appear to apply to both overall and symptomatic infection risk. Together, the results suggest that specific antibodies can predict relative infection risk in pediatric populations with diverse immune histories. Understanding these immune correlates may inform tailored vaccination strategies and risk assessments as SARS-CoV-2 continues to evolve.