Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine

OVX836 is a recombinant protein-based vaccine targeting the highly conserved influenza nucleoprotein (NP), which aims to confer a broad-spectrum protection against influenza. In a Phase 1 study, OVX836, administered intramuscularly, has been found safe and immunogenic. The 90 mu g and 180 mu g dose levels were selected to be further evaluated in this randomized, monocenter, reference-controlled (Influvac Tetra (TM): quadrivalent seasonal influenza subunit vaccine), parallel group, double-blind, Phase 2a study in 300 healthy volunteers, aged 18-65 years, during the 2019/2020 flu season. Safety, influenza-like illness episodes (ILI; based on the Flu-PRO (R) questionnaire) and immunogenicity were assessed up to 180 days post-vaccination. OVX836 was safe and presented a reactogenicity profile similar to Influvac Tetra. It induced a significant increase in terms of NP-specific interferon-gamma (IFN gamma) spot forming cells (SFCs), NP-specific CD4+ T-cells (essentially polyfunctional cells) and anti-NP IgG responses. OVX836 was superior to Influvac Tetra for all immunological parameters related to NP, and the 180 mu g dose was significantly superior to the 90 mu g dose for SFCs and CD4+ T-cells expressing IFN gamma. Both the CD4+ T-cell and the anti-NP IgG responses persisted up to Day 180. An efficacy signal was observed with OVX836 at 180 mu g through reduction of ILI episodes occurring during the flu season as of 14 days post-vaccination. In conclusion, these results encourage further clinical evaluation of OVX836 in order to confirm the signal of efficacy on ILIs and/or laboratory-confirmed influenza cases.