Double-Blind, Randomized, Phase 2a Study to Evaluate the Safety and Immunogenicity of OVX836, a Nucleoprotein-Based Universal Influenza Vaccine, Co-Administered with Fluarix Tetra® or Afluria Quad®

Background/Objectives: For decades, influenza vaccine development has focused on eliciting antibody responses. Increasing evidence suggests that cell-mediated immune (CMI) responses can complement the humoral response by providing broader protection. This study evaluated the safety and immunogenicity of an experimental nucleoprotein (NP)-based vaccine, OVX836, when co-administered with a licensed hemagglutinin (HA)-based inactivated split influenza vaccine (IIVs; either Fluarix Tetra® [Fluarix] or Afluria Quad® [Afluria]). Methods: This randomized, double-blind, phase 2a study (ClinicalTrials.gov: NCT05734040) included six groups, each of approximately 80 healthy adults (18–60 years old). Participants received either a) OVX836 (480 μg) concomitantly administered with Fluarix, Afluria, or placebo, b) Fluarix or Afluria concomitantly administered with placebo, or c) double placebo (double-dummy approach). Treatments were administered concomitantly by intramuscular injection into the deltoid muscles of opposite arms. Endpoints included reactogenicity, safety, and immunogenicity, measured by hemagglutination inhibition assay (HAI), anti-NP immunoglobulin G (IgG), and NP-specific CMI. Results: Concomitant administration of OVX836 with Fluarix or Afluria was safe and well tolerated. HAI responses to the IIV strains were similar when administered with OVX836 or placebo. Groups receiving OVX836 demonstrated markedly enhanced humoral anti-NP IgG and NP-specific CMI responses, which were negligible in the non-OVX836 groups. No evidence of clinically significant immunological interference between OVX836 and IIVs was observed for any endpoint. Conclusions: Concomitant administration of OVX836 did not adversely affect IIV safety or HAI responses, while inducing robust anti-NP IgG and NP-specific CMI responses. These findings support further clinical development of OVX836 in combination with licensed IIVs.