Safety and Immunogenicity of Inactivated Bacillus subtilis Spores as a Heterologous Antibody Booster for COVID-19 Vaccines

Abstract

The coronavirus diseases 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have threatened the world for more than 2 years. Multiple vaccine candidates have been developed and approved for emergency use by specific markets, but multiple doses are required to maintain the antibody level. Preliminary safety and immunogenicity data about an oral dose vaccine candidate using recombinant Bacillus subtilis in healthy adults were reported previously from an investigator-initiated trial in Hong Kong. Additional data are required in order to demonstrate the safety and efficacy of the candidate as a heterologous booster in vaccinated recipients. In an ongoing, placebo-controlled, observer-blinded, fixed dose, investigator-initiated trial conducted in the Macau, we randomly assigned healthy adults, 21 to 62 years of age to receive either placebo or a Bacillus subtilis oral dose vaccine candidate, which expressed the spike protein receptor binding domain of SARS-CoV-2 on the spore surface. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. For both the active vaccine and placebo, participants received three courses in three consecutive days. A total of 16 participants underwent randomization: 9 participants received vaccine and 7 received placebo. No observable local or systemic side-effect was reported. In both younger and older adults receiving placebo, the neutralizing antibody levels were gradually declining, whereas the participants receiving the antibody booster showed an increase in neutralizing antibody level.