Phase 1, first-in-human, randomized, placebo-controlled, dose-escalating study to evaluate OVX033, a...

Area of Science:

• Vaccinology
• Immunology
• Infectious Diseases

Background:

• OVX033 is a universal sarbecovirus vaccine candidate targeting the conserved SARS-CoV-2 nucleocapsid (N) protein.
• Preclinical data indicated cross-variant protection and good tolerability.
• This study assessed the safety and immunogenicity of a single intramuscular dose in healthy adults.

Purpose of the Study:

• To evaluate the safety and immunogenicity of OVX033 in a first-in-human trial.
• To assess reactogenicity and adverse events following vaccination.
• To measure anti-N IgG and N-specific T-cell responses post-vaccination.

Main Methods:

• A randomized, placebo-controlled, observer-blind, dose-escalation study.
• 48 participants received OVX033 (100µg, 250µg, or 500µg) or placebo.
• Safety assessments included reactogenicity and adverse events; immunogenicity measured anti-N IgG and T-cell responses.

Main Results:

• OVX033 was safe and well-tolerated across all dose levels.
• Common side effects included injection site pain, fatigue, headache, and myalgia.
• A robust anamnestic anti-N IgG response was observed, with 67-100% showing 4-fold rises; modest CD4+ T-cell responses were noted, but CD8+ responses were limited.

Conclusions:

• OVX033 demonstrated a favorable safety profile and boosted pre-existing humoral immunity.
• A N-specific T-cell-mediated immune response was achieved but was of limited amplitude.
• A two-dose regimen or adjuvantation may enhance the T-cell response.