372. Co-Administration of OVX836, NP-Based Universal Influenza Vaccine Candidate, with Conventional HA-Based Influenza Vaccine: Results of Phase 2a Clinical trial

Abstract

Abstract Background Quadrivalent Inactivated Influenza Vaccine (QIV) generate antibody responses mostly directed against the highly mutating hemagglutinin. An alternative path for influenza vaccination is to generate cellular immunity to well-conserved nucleoprotein (NP), which has been associated with protection against influenza disease. OVX836 is an unadjuvanted recombinant vaccine targeting NP. We have previously shown that OVX836 induces strong, dose-dependent NP-specific T and B-cell immune responses in human, with a signal for efficacy of 84% (95%CI=17%-97%), together with synergistic protection with QIV in preclinical models. Here, we investigate in human the concomitant administration of OVX836 with QIV. Methods Phase 2a, randomized, double-blind, controlled, study to evaluate immunogenicity and safety of the concomitant administration of OVX836 and QIV in healthy adults (18-55 years) as 2 separate injections into the same arm, compared to (i) QIV and (ii) OVX836. Results Safety: All three treatments were safe and well tolerated. All occurrences of local and/or systemic signs and symptoms were mild or moderate in severity, except for one severe fatigue and myalgia in the QIV group and one severe headache in the OVX836 group. Immunogenicity: Primary endpoint was achieved for the QIV and the OVX836+QIV, which triggered adequate immune response to the QIV (Hemagglutination Inhibition - HAI). Geometric mean fold-rise at Day 29 vs Day 1 of the HAI were similar between the QIV and OVX836+QIV groups for all strains contained in the QIV (figure 1). While there was an increase in NP-specific T-cell IFN-γ ELISPOT response at Day 8 for the OVX836 and the OVX836+QIV groups compared to QIV (p< 0.0001, Wilcoxon rank-sum test), no significant difference was observed in terms of change (D8-D1) between OVX836 and OVX836+QIV – figure 2. The analysis of additional NP-specific immune parameters supports similar conclusion, with no to very limited immune interference between vaccines.Figure 1:Geometric Mean Ratio of HAI for each strain of the QIV between D1 and D29Figure 2:Mean Change (+Standard Deviation) of IFNg ELISpot response b/w D1 and D8 Conclusion OVX836 co-administered with QIV was safe, with no immune interference on either HAI or NP-specific IFN-γ ELISPOT, thus warranting further evaluation in larger trials. Disclosures Paul Willems, n/a, Osivax: Advisor/Consultant Jessika Tourneur, n/a, Osivax: Stocks/Bonds Delphine Guyon-Gellin, n/a, Osivax: Stocks/Bonds Alexandre Le Vert, Osivax: Board Member|Osivax: Stocks/Bonds Florence Nicolas, n/a, Osivax: Stocks/Bonds