Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months.

BACKGROUND: Respiratory syncytial virus (RSV) remains a leading cause of pediatric morbidity, with no approved vaccine. We assessed the safety and immunogenicity of the Ad26.RSV.preF vaccine candidate in adults and children. METHODS: In this randomized, double-blind, phase 1/2a, placebo-controlled study, 12 adults (18-50 years) and 36 RSV-seropositive children (12-24 months) were randomized 2:1 to Ad26.RSV.preF (1 × 1011 viral particles [vp] for adults, 5 × 1010 vp for children) or placebo, at day 1 and 29, with 6-month immunogenicity and 1-year safety follow-up. Respiratory syncytial virus infection was an exploratory outcome in children. RESULTS: In adults, solicited adverse events (AEs) were generally mild to moderate, with no serious AEs. In children, no vaccination-related serious AEs were reported; fever was reported in 14 (58.3%) Ad26.RSV.preF recipients. Baseline pediatric geometric mean titers for RSV A2 neutralization increased from 121 (95% confidence interval [CI], 76-191) to 1608 (95% CI, 730-3544) at day 29, and 2235 (95% CI, 1586-3150) at day 57, remaining elevated over 7 months. Respiratory syncytial virus infection was confirmed in fewer children receiving Ad26.RSV.preF (1, 4.2%) than placebo (5, 41.7%). CONCLUSIONS: Ad26.RSV.preF demonstrated immunogenicity in healthy adults and toddlers, with no safety concerns raised. Evaluations in RSV-seronegative children are underway.

Non-inferiority of mammalian cell-derived quadrivalent subunit influenza virus vaccines compared to trivalent subunit influenza virus vaccines in healthy children: a phase III randomized, multicenter, double-blind clinical trial.

OBJECTIVES: The safety and immunogenicity of mammalian cell-derived quadrivalent influenza vaccine (QIVc) as compared with trivalent influenza vaccines (TIV1c/TIV2c) was evaluated in children aged ≥4 to <18 years. METHODS: Two thousand three hundred and thirty-three subjects were randomized 2:1:1 to receive either one or two doses of study vaccine depending on previous vaccination status. Hemagglutination inhibition antibody responses for all four influenza strains were performed 3 weeks after the last dose. Reactogenicity and safety were also assessed (ClinicalTrials.gov: NCT01992107). RESULTS: QIVc met the non-inferiority criteria against all four vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B lineage included in the comparator vaccines, when geometric mean titers and seroconversion rates were compared at 3 weeks after the last vaccination. Similar percentages of subjects experienced solicited and unsolicited adverse events (AEs) across all subgroups. Unsolicited AEs, serious AEs, medically attended AEs, and new onset chronic disease were reported in comparable percentages of subjects in all study groups. No vaccine-related serious AEs or deaths occurred. CONCLUSIONS: QIVc demonstrated a similar safety profile and immunogenicity responses against all four vaccine strains without signs of immune interference on addition of an alternate lineage B strain compared with TIV1c/TIV2c and may provide broader protection against both influenza B lineages in children.