Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers.

BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).

Prevalence of respiratory viruses in community-acquired pneumonia in children: a systematic review and meta-analysis.

BACKGROUND: Respiratory viruses are increasingly detected in children with community-acquired pneumonia but prevalence estimates vary substantially. We aimed to systematically review and pool estimates for 22 viruses commonly associated with community-acquired pneumonia. METHODS: We conducted a systematic review and meta-analysis to determine the prevalence of each of the common respiratory viruses detected by any diagnostic method in children aged up to 18 years with community-acquired pneumonia. We searched MEDLINE, PubMed, Embase, Web of Science, and Scopus databases with no language restrictions for relevant published articles and reports published between Jan 1, 1995, and Dec 31, 2019, restricting the review to pre-COVID-19 pandemic years. Three independent reviewers screened articles and extracted data using a predefined protocol. We calculated the pooled prevalence for each virus in childhood pneumonia using DerSimonian-Laird random-effects models. We assessed bias using the Newcastle-Ottawa Scale. The review protocol was registered in PROSPERO (CRD42016034047). FINDINGS: We identified 186 eligible articles that represented 152 209 children up to age 18 years with community-acquired pneumonia. One or more respiratory viruses were detected in 55·0% (95% CI 50·4-59·7) of paediatric patients with a diagnosis of community-acquired pneumonia; heterogeneity was high (I2=99·4%). Respiratory syncytial virus (22·7%, 20·9-24·5) and rhinovirus (22·1%, 19·5-24·7) were the most commonly detected causes of paediatric pneumonia globally, with other viruses detected in 1-9% of cases. There was non-significant variation in prevalence by the country's national income, under-5 mortality rate, or WHO region. INTERPRETATION: Respiratory viruses are frequently detected in community-acquired pneumonia among children of all ages and geographical regions, with non-significant variation by country's national income or region. Further strategies to limit antibiotic use in children with viral pneumonia and develop treatment and prevention approaches targeting common respiratory viruses are expected to have a substantial effect on the residual burden of childhood pneumonia. FUNDING: None.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Persistence of the Immune Responses and Cross-Neutralizing Activity With Variants of Concern Following 2 Doses of Adjuvanted SCB-2019 Coronavirus Disease 2019 Vaccine.

BACKGROUND: We have previously reported the safety and immunogenicity 4 weeks after 2 doses of the Clover coronavirus disease 2019 (COVID-19) vaccine candidate, SCB-2019, a stabilized prefusion form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S-trimer). We now report persistence of antibodies up to 6 months after vaccination, and cross-neutralization titers against 3 variants of concern (VoCs). METHODS: In a phase 1 study, adult (18-54 years of age) and elderly (55-75 years of age) volunteers received 2 vaccinations 21 days apart with placebo or 3-, 9-, or 30-µg. We measured immunoglobulin G (IgG) antibodies against SCB-2019, angiotensin-converting enzyme 2 (ACE2) competitive binding antibodies, and neutralizing antibodies against wild-type SARS-CoV-2 (Wuhan-Hu-1) at days 101 and 184, and neutralizing antibodies against 3 VoCs, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1), in day 36 sera. RESULTS: Titers waned from their peak at days 36-50, but SCB-2019 IgG antibodies, ACE2 competitive binding antibodies, and neutralizing antibodies against wild-type SARS-CoV-2 persisted at 25%-35% of their observed peak levels at day 184. Day 36 sera also demonstrated dose-dependent increases in neutralizing titers against the 3 VoCs. CONCLUSIONS: SCB-2019 dose-dependently induced immune responses against wild-type SARS-CoV-2, which persisted up to day 184. Neutralizing antibodies were cross-reactive against 3 of the most prevalent VoCs.