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 This was a randomized, placebo-controlled, double-blind, dose-escalating, single center first-in-human study, conducted in 36 healthy adults aged 18-49 years. Twelve subjects per cohort (9 vaccine and 3 placebo) received two 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 1 st and 2 nd 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 1 st vaccination. The 2 nd 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.

Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine

“…A single IM injection of 90µg or 180µg of the OVX836 vaccine candidate was safe and well-tolerated. This confirms the observations made during the Phase 1 study ( 19 ). The overall safety profile, in terms of nature, intensity and duration of local and systemic signs and symptoms, was very similar to that of the tetravalent reference vaccine Influvac Tetra.…”

“…The IFNγ SFC response remained significantly higher than the baseline value 6 months after the immunization when excluding the subjects situated in the highest quartile who had probably been exposed to influenza before vaccination (Day 1). As already observed in Phase 1 study ( 19 ), the OVX836-induced T-cells peaked one week after vaccination and decreased afterwards while remaining above baseline at Day 180. The kinetics of the vaccine-induced NP-specific T-cell response is consistent with that observed after influenza infection and corresponds to the expansion and contraction phases described for T-cell responses ( 10 , 32 – 34 ).…”

“…The results of a Phase 1, randomized, placebo-controlled clinical study have recently been published ( 19 ). When administered by the intramuscular (IM) route, OVX836 was safe and well-tolerated at 30µg, 90µg and 180µg, administered as a two-dose schedule with one month interval.…”

Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response

“…Recently, a phase I clinical trial of OVX836 in adults showed no adverse events across administrations or dosage levels. The study also showed increased NP-specific IFN-γ T cells and IgG titers at first dose, however, immune response was not further increased at the second dose ( 246 ). Overall, NP-based recombinant vaccines showed potential as a main or component antigen in inducing CD8 + T-cell responses crucial for heterosubtypic immunity in universal influenza vaccine development.…”

The role of cell-mediated immunity against influenza and its implications for vaccine evaluation

“…Recently, several human observational studies and pre-clinical studies reported that CD4 + and/or CD8 + T-cells specific to NP epitopes could provide additional protection ( 26 , 27 , 165 , 166 ). OVX-836, a recombinant influenza vaccine developed by Osivax (Lyon, France), contains seven copies of the target antigen (NP) fused to the patented heptameric oligomerization domain (oligoDOM ® ) ( 167 ). Oligomerization of antigens has been proven to induce improved humoral and cellular immune responses in animals ( 168 , 169 ).…”