Abstract
Abstract
Background
An effective RSV vaccine which elicits active immunity and lasting protection could have a significant impact on child health. This study evaluated safety and immunogenicity of three intranasal live-attenuated candidate RSV vaccines, RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and RSV/276 to placebo.
Methods
Healthy, RSV-seronegative children 6-24 months of age were randomized to receive one of three candidate vaccines or placebo in a blinded manner. Participants were monitored for vaccine reactogenicity and RSV serum antibodies and over the subsequent RSV season.
Results
Between years 2019 and 2023, 67 participants were randomized, including 20 each to RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and placebo arms and seven to the RSV/276 arm. The RSV/276 arm was closed early due to an excess of mild cough events in another study. The proportion (95% confidence interval) of children who experienced at least one solicited an adverse event during the 28 days after inoculation was 55% (32%, 77%) in the RSV/ΔNS2/Δ1313/I1314L arm, 40% (19%, 64%) in the RSV/6120/ΔNS2/1030s arm, 71% (29%, 96%) in the RSV/276 arm, and 55% (32%, 77%) in the placebo arm. Events were mostly Grade 1 and were often associated with other viruses. The proportion of children with a ≥4-fold increase in serum RSV-neutralizing antibody titer in each of the candidate vaccine arms (>70%) was significantly greater than in the placebo arm (15%).
Conclusions
RSV/ΔNS2/Δ1313/I1314L and RSV/6120/ΔNS2/1030s had excellent safety and immunogenicity; the assessment of RSV/276 was limited by the small sample size. RSV/ΔNS2/Δ1313/I1314L and RSV/6120/ΔNS2/1030s were deemed suitable for further evaluation.