Safety and Immunogenicity of OVX836, a Nucleoprotein-Based Universal Influenza Vaccine, Co-Administered with Fluarix® Tetra, a Seasonal Hemagglutinin-Based Vaccine

<b>Background/Objectives</b>: The combination of a hemagglutinin antigen (HA)-based inactivated influenza vaccine (IIV; Fluarix^® Tetra; GlaxoSmithKline) with a nucleoprotein (NP)-based vaccine, such as OVX836, should increase the efficacy of influenza vaccines since it leverages two complementary immunological mechanisms: HA antibodies targeting the virus envelope and neutralizing it, and an NP cell-mediated immune (CMI) response destroying infected cells. <b>Methods</b>: This was a randomized, double-blind, Phase 2a study (ClinicalTrials.gov NCT05284799) including three groups of 60 healthy subjects (18-55 years old) receiving either IIV + placebo, IIV + OVX836 (480 µg), or OVX836 + placebo intramuscularly and concomitantly into the same deltoid muscle. The endpoints were reactogenicity, safety, and immunogenicity (hemagglutination inhibition assay [HAI], anti-NP immunoglobulin G [IgG], and NP-specific cell-mediated immunity [CMI]). <b>Results</b>: The co-administration of IIV + OVX836 was safe and well-tolerated. The HAI response was strong and similar in the two IIV groups with no interference of OVX836. The humoral anti-NP IgG and NP-specific CMI responses to OVX836 were strong in the two OVX836 groups, and no major interference of IIV was observed. <b>Conclusions</b>: This study supports further clinical development of OVX836 as a combined IIV/OVX836 seasonal vaccine capable of inducing robust and complementary HAI and CMI NP-specific responses.