Live-Attenuated Vaccines Prevent Respiratory Syncytial Virus-Associated Illness in Young Children

Abstract

To determine the preliminary efficacy and durability of live-attenuated respiratory syncytial virus RSV vaccine candidates from phase 1 clinical trials.Healthy RSV-naïve children aged 6 to 24 months (n = 241) were randomly assigned 2:1 to receive either a live-attenuated RSV vaccine or placebo.Separate trials of 7 different RSV vaccine candidates were similarly conducted, and data were pooled for analysis. The surveillance period was from ∼5.5 to 13 months after day 56 postvaccination. The RSV neutralizing antibody (NeutAb) response, also considered indicative of vaccine efficacy, was defined as more than a fourfold increase in complement-enhanced plaque reduction-neutralizing antibody titers after vaccination. Data were further grouped by “more promising” vaccines (NeutAb response in ≥80% of vaccine recipients; n = 5) and “less promising” (NeutAb response in ≤59% of vaccines; n = 2).There was 66% efficacy against respiratory syncytial virus–associated medically attended acute respiratory illness (RSV-MAARI) infections (P = .007) and 100% efficacy against respiratory syncytial virus–associated medically attended acute lower respiratory illness (RSV-MAALRI) (P = .009) among all NeutAb responders. A NeutAb response overall was significantly associated with protection against RSV-MAARI and RSV-MAALRI (odds ratio: 0.26; 95% confidence interval: 0.09 to 0.75; P = .014). Vaccine virus titers shed by vaccine recipients did not correlate with protection against RSV-MAARI or RSV-MAALRI. Although there was no significant difference in the primary NeutAb responses between the vaccinated and placebo groups (P = .21), the magnitude of anamnestic NeutAb response was ∼10-fold higher in vaccine recipients than in those with the placebo after infection with wild-type RSV during surveillance (P = .0001). In the vaccinated group not infected with wild-type RSV (n = 89), the postsurveillance anamnestic NeutAb titers (79 [6.3 log2]) were less than postimmunization (111 [6.8 log2]; P < .001); however, the absolute difference was small. On the basis of the disease rate model, the authors determined that future study sample sizes between 540 and 1300 would be needed to demonstrate efficacy.Live-attenuated RSV vaccines provide protection against acute respiratory and lower respiratory illnesses and can produce durable response.Currently, palivizumab, a monoclonal antibody, is still the only Food and Drug Administration–approved medication for RSV, providing short-term prophylaxis against severe RSV disease in high-risk infants and children with preexisting conditions, such as prematurity with or without bronchopulmonary dysplasia. The preliminary data from these small clinical trials identifying these “more promising” vaccines suggest that we may be 1 step closer toward actually developing an RSV vaccine that can protect against infection and address the burden of RSV disease. Obvious considerations for future and later stage clinical trials include appropriately powered sample sizes (including RSV-exposed subjects), study duration, geographic locations, timing of the RSV season, and vaccine delivery routes and dosing.