Safety and immunogenicity of a booster dose of COVAC-2, a Sepivac SWE™ adjuvanted SARS-CoV-2 recombinant protein vaccine in previously vaccinated healthy adults; a randomized controlled multicentre trial.

This Phase 1 clinical trial evaluated the safety and immunogenicity of COVAC-2, a recombinant protein subunit vaccine as a heterologous booster in adults previously immunized with authorized COVID-19 vaccines (NCT05226702). COVAC-2 contains the SARS-CoV-2 S1 spike protein subunit adjuvanted with Sepivac SWE™, an open-access oil-in-water adjuvant. Sixty participants were randomized to receive a single intramuscular dose of COVAC-2 (10 µg or 25 µg) or placebo, with follow-up through Day 180. The vaccine was well tolerated, with most adverse events being mild or moderate; no serious adverse events were attributed to vaccination. Immunogenicity assessments included spike-binding antibody ELISA, pseudovirus neutralization assays (PNA), ELISpot, and flow cytometry. The 25 µg dose elicited the strongest humoral and cellular responses, with peak antibody titers observed 14 d after COVAC-2 vaccination. While titers waned, they were sustained above baseline through Day 180. ELISpot and flow cytometry revealed elevated IFN-γ and IL-2 responses indicating antigen-specific T-cell activation. Minimal IL-4 and IL-13 responses were demonstrated by flow cytometry. These findings support the safety and immunogenicity of COVAC-2 as a heterologous booster, particularly at the 25 µg dose level. The favorable safety profile, induction of immune responses, and thermal stability of the vaccine formulation suggest its potential utility in global vaccination strategies, especially in low- and middle-income countries. COVAC-2 may offer a scalable and accessible platform for enhancing protection against COVID-19.Clinicaltrials.gov: NCT05226702 - Registered 22 Jul 2022.