Phase 1 Randomized, Placebo-Controlled, Dose-Escalating Study to Evaluate OVX836, a Nucleoprotein-Based Influenza Vaccine: Intramuscular Results

Abstract

Background. OVX836 is a recombinant protein vaccine targeting the highly conserved influenza nucleoprotein (NP), which could confer broad-spectrum protection against this disease. Methods. A randomized, placebo-controlled, double-blind, dose-escalating, single- center, first-in-human study was conducted in 36 healthy adults aged 18–49 years. Twelve subjects per cohort (9 vaccine and 3 placebo) received 2 OVX836 intramuscular administrations on days 1 and 28 at the dose level of 30 µg, 90 µg, or 180 µg. Safety and immunogenicity were assessed after each vaccination and for 150 days in total. Results. OVX836 was safe and well tolerated at all dose levels, with no difference in solicited local and systemic symptoms, and unsolicited adverse events between the first and second administration, or between dose levels. All subjects presented pre-existing NP-specific immunity at baseline. OVX836 induced a significant increase in NP-specific interferon-gamma T cells and anti-NP immunoglobulin G at all dose levels after the first vaccination. The second vaccination did not further increase the response. There was a trend for a dose effect in the immune response. Conclusions. The safety and reactogenicity profile, as well as the humoral and cellular immune responses, encourage further evaluation of OVX836 in a larger Phase 2a study.