Live respiratory syncytial virus attenuated by M2-2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children.

McFarland, Elizabeth J; Karron, Ruth A; Muresan, Petronella; Cunningham, Coleen K; Libous, Jennifer; Perlowski, Charlotte; Thumar, Bhagvanji; Gnanashanmugam, Devasena; Moye, Jack; Schappell, Elizabeth; Barr, Emily; Rexroad, Vivian; Fearn, Laura; Spector, Stephen A; Aziz, Mariam; Cielo, Mikhaela; Beneri, Christy; Wiznia, Andrew; Luongo, Cindy; Collins, Peter; Buchholz, Ursula

BACKGROUND The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV RNA synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. METHODS RSV-seronegative children ages 6-24 months received one intranasal dose of 105 plaque forming units (PFU) of LID/ΔM2-2/1030s (n=21) or placebo (n=11) (NCT02952339/ NCT02794870). RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically-attended acute respiratory illness (MAARI) and pre- and post-surveillance serum antibody titers were monitored. RESULTS Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immuno-plaque assay; 5.1 log10 copies/mL by RT-qPCR) and had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had >4-fold increases in antibody titers post-surveillance without RSV-MAARI, indicating anamnestic responses without significant illness following infection with community-acquired RSV. CONCLUSION LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.