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

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BACKGROUND: This 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 SWE™. METHODS: Healthy adults (n = 61) with no known prior exposure to SARS-CoV-2 virus or vaccines 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). Participants in both cohorts were randomized to a two-dose schedule of 25 μg, 50 μg, or 100 μg (cohort 1 only) of COVAC-2 vaccine, or placebo on Days 0 and 28. Safety and immunogenicity data were collected from study Day 0 to 365. RESULTS: The most common adverse events were injection site pain, generalized muscle aches, and headaches in all dose levels and age groups. Most events were grade 1 and 2 in severity but one participant in the 100 μg dose group reported grade 3 adverse events. S1 subunit-specific humoral binding and neutralizing antibody titres peaked with a geometric mean of 817 IU/mL and 168 IU/mL, respectively, in groups vaccinated with COVAC-2 between study Day 42 and 56 and then decreased in the absence of authorized vaccine administration or infection with SARS-CoV-2. Seroconversion in both 18-54 and 55+ cohorts required two doses of vaccine with 100 % of participants seroconverting by Day 42 in the 18-54 cohort and 88 % of participants by Day 42 in the 55+ cohort. 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. CONCLUSIONS: This Phase 1 trial indicated that COVAC-2 is safe and induces high levels of both antigen-specific binding and neutralizing antibodies by Day 42-56 with levels beginning to wane by Day 120.