Phase 1, first-in-human, randomized, placebo-controlled, dose-escalating study to evaluate OVX033, a nucleocapsid-based SARS-CoV-2 candidate vaccine
Odile Launay, Emilie Piat, Olivia Bonduelle, Jacques Bruhwyler, Liem Binh Luong, Michèle Wokam, Jessika Tourneur, Philippe Moris, Béatrice Parfait, Cécile Paques, Thalia Garcia Téllez, Christophe Combadière, Alexandre Boissonnas, Alexandre Le Vert, Nicola Groth, Florence NicolasAbstract
Background
OVX033 is a potential universal sarbecovirus vaccine candidate targeting the highly conserved SARS-CoV-2 nucleocapsid (N) protein. Preclinical studies have demonstrated cross-variant protection and favorable tolerability. This first-in-human trial evaluated the safety and immunogenicity of a single intramuscular dose of OVX033 in healthy adults (18-49 years).
Methods
In this randomized, placebo-controlled, observer-blind, sequential, dose-escalation study, 48 participants, previously vaccinated with SARS-CoV-2 licensed vaccines, received either OVX033 (100µg, 250µg or 500µg; n=12 per cohort) or placebo (n=12, 4 per cohort). Solicited reactogenicity was recorded for 7 days, unsolicited adverse events (AEs) for 28 days, and serious AEs (SAEs) for 6 months. Immunogenicity assessments included anti-N IgG and N-specific T-cell responses.
Results
OVX033 was safe and well-tolerated whatever the dose-level. Injection site pain was the most common local reaction; fatigue, headache, and myalgia were the most frequent systemic symptoms. No severe reactogenicity, treatment-related SAEs, or safety signals were identified. OVX033 elicited a robust anamnestic anti-N IgG response, with titers peaking at Day 29, and 4-fold rises versus baseline observed in 67–100% of vaccinees. Modest increases of N-specific IFNγ CD4+ T-cell responses were measured on Days 8 and 29 after vaccination, while CD8+ T-cell responses remained below the limit of quantification. No clear OVX033 dose-effect was evidenced.
Conclusions
OVX033 demonstrated a favorable safety profile and strong boosting of pre-existing N-specific humoral immunity. Although a N-specific T-cell-mediated immune response was achieved, it remained of limited amplitude. This limitation could be addressed by implementing a two-dose regimen, or through the adjuvantation of the vaccine.