Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine

Simple Summary V-306 is a synthetic virus-like particle-based vaccine candidate displaying multiple respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm) as an antigenic epitope. This first-in-human, double-blind, placebo-controlled, dose-escalating study in healthy young women showed that it was safe and induced an increase in immunoglobulin G specific of FsIIm. This did not translate into an increase in RSV-neutralizing antibody titers, which were already high at baseline. Background: V-306 is a virus-like particle-based vaccine candidate displaying respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm) as an antigenic epitope. Methods: This was a randomized, placebo-controlled, double-blind, dose-escalating, first-in-human study, conducted in 60 women aged 18-45 years. Twenty subjects per cohort (15 vaccine and five placebo) received two V-306 intramuscular administrations on Days 0 and 56 at 15 mu g, 50 mu g, or 150 mu g. Safety and immunogenicity were assessed after each vaccination and for 1 year in total. Results: V-306 was safe and well tolerated at all dose levels, with no increase in reactogenicity and unsolicited adverse events between the first and second administrations. At 50 mu g and 150 mu g, V-306 induced an increase in FsIIm-specific immunoglobulin G (IgG) titers, which lasted at least 4 months. This did not translate into an increase in RSV-neutralizing antibody titers, which were already high at baseline. No increase in the anti-F protein-specific IgG titers was observed, which were also high in most subjects at baseline due to past natural infections. Conclusions: V-306 was safe and well-tolerated. Future modifications of the vaccine and assay conditions will likely improve the results of vaccination.

Automated summary

V-306, a synthetic virus-like particle-based vaccine candidate, displaying multiple respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm), was found to be safe and induced an increase in immunoglobulin G specific to FsIIm in a study on healthy young women. However, this did not result in an increase in RSV-neutralizing antibody titers, which were already high at baseline.