Live-Attenuated Intranasal RSV Vaccine in Infants and Toddlers

Abstract

Background: RSV/ΔNS2/Δ1313/I1314L (RSVt) (Sanofi) is a candidate live-attenuated intranasal respiratory syncytial virus (RSV) vaccine for infants and toddlers.

Methods: This phase I/II randomized clinical trial, conducted at sites in the United States (N=22), Chile (N=2), and Honduras (N=2), enrolled participants 6-18 months of age in four cohorts. In cohort 4, the primary cohort reported in this article, participants were randomly assigned to receive vaccinations on days 0 and 56 of either low-dose (LD) RSVt, high-dose (HD) RSVt, or placebo. Primary safety end points included: unsolicited systemic adverse events 30 minutes post vaccination, and solicited site and systemic reactions 28 days post vaccination. The primary immunogenicity end points were the geometric mean titers of RSV A serum neutralizing antibody after vaccinations 1 (day 56) and 2 (day 84) among RSV-naive participants at baseline.

Results: Among 180 participants (LD, N=61; HD, N=58; placebo, N=61), 115 were RSV-naive at baseline (LD, N=45; HD, N=32; placebo, N=38). No unsolicited systemic adverse events occurred within 30 minutes post vaccination in the LD or HD groups. Solicited site reactions were reported by 83.1%, 74.5%, and 68.9% of participants post vaccination 1, and 75.6%, 77.8%, and 55.6% post vaccination 2, in the LD, HD, and placebo groups, respectively. Solicited systemic reactions were reported by 79.7%, 73.2%, and 77.0% of participants post vaccination 1, and 66.7%, 66.7%, and 48.1% post vaccination 2, in the LD, HD, and placebo groups, respectively. Neutralizing antibody titers among RSV-naive participants were 83.7 (95% confidence interval (CI), 49.5 to 142.0), 79.4 (95% CI, 47.2 to 134.0), and 20.6 (95% CI, 16.4 to 25.9) post vaccination 1, and 142.0 (95% CI, 86.4 to 232.2), 107.0 (95% CI, 70.0 to 163.0), and 26.3 (95% CI, 18.8 to 37.0) post vaccination 2, in the LD, HD, and placebo groups, respectively.

Conclusions: The RSVt vaccine demonstrated promising immunogenicity profiles at both LD and HD strengths among infants and toddlers, without identified safety concerns. (Funded by Sanofi; ClinicalTrials.gov number, NCT04491877).