Safety and Immunogenicity of Covac-2, a Sepivac Swe™ Adjuvanted Sars-Cov-2 Recombinant Protein Vaccine in Healthy Adults; a Randomized Controlled First-in-Human Dose-Escalation Trial

BackgroundThis first-in human dose-escalating, randomized, placebo-controlled, observer-blinded study assessed the safety and immunogenicity of a recombinant protein vaccine (COVAC-2) composed of the S1 subunit of the spike protein of SARS-CoV-2 formulated with the oil-in-water adjuvant Sepivac SWETM.MethodsHealthy adults (n=61) were enrolled into one of two cohorts, based on age, 18-54 years old (n=34, Cohort 1) or 55+ years (n=27, Cohort 2). Cohort 1 was subdivided into groups receiving either 25 µg, 50 µg, or 100 µg of COVAC-2 vaccine, or placebo, while Cohort 2 was subdivided into groups receiving either 25 µg or 50 µg of COVAC-2 vaccine, or placebo. Administrations were provided on study Days 0 and 28. Safety and immunogenicity data were collected from both cohorts until study Day 365.ResultsGrade 1 and 2 local or systemic adverse events were observed in the placebo, 25 µg and 50 µg groups, while one participant in the 100 µg dose group reported grade 3 adverse events after both the first and second dose. The main adverse events reported include injection site pain, generalized muscle aches, and headaches in all dose levels and age groups. S1 subunit-specific humoral binding and neutralizing antibody titres peaked between study Day 42 and 56 and then decreased in the absence of authorized vaccine administration or infection with SARS-CoV-2. No clear T cell response was detected when measuring IFNγ or IL-5 in peripheral blood mononuclear cells following stimulation with SARS-CoV-2 peptides.ConclusionsThe results of this Phase 1 trial indicate that COVAC-2 is safe and induces high levels of both antigen-specific binding and neutralizing antibodies.