Evaluation of Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV/Delta NS2/Delta 1313/I1314L and RSV/276 in RSV-Seronegative Children

Two promising live-attenuated RSV candidate vaccines, RSV/Delta NS2/Delta 1313/I1314L and RSV/276, were evaluated in 65 healthy children aged 6-24 months. Both products were restricted in replication; however, RSV/276 recipients had excess cough events. RSV/Delta NS2/Delta 1313/I1314L is a candidate for further clinical evaluation. Background This United States-based study compared 2 candidate vaccines: RSV/Delta NS2/Delta 1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion. Methods RSV-seronegative children aged 6-24 months received RSV/Delta NS2/Delta 1313/I1314L (10(6) plaque-forming units [PFU]), RSV/276 (10(5) PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season. Results Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/Delta NS2/Delta 1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/Delta NS2/Delta 1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/Delta NS2/Delta 1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had >= 4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased >= 4-fold in 60% and 92% of RSV/Delta NS2/Delta 1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses. Conclusions Both vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses.