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: see text] [Figure: see text] 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