Retraction: Sung et al. Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate. Vaccines 2022, 10, 2.

The journal retracts the article "Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate"[...].

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

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.

Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate.

Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have been developed to prevent SARS-CoV-2 infection. Although some of them have already been approved under the COVID-19 pandemic, various drawbacks, including severe side effects and the requirement for sub-zero temperature storage, may hinder their applications. Bacillus subtilis (B. subtilis) is generally recognized as a safe and endotoxin-free Gram-positive bacterium that has been extensively employed as a host for the expression of recombinant proteins. Its dormant spores are extraordinarily resistant to the harsh environment in the gastrointestinal tract. This feature makes it an ideal carrier for oral administration in resisting this acidic environment and for release in the intestine. In this study, an engineered B. subtilis spore expressing the SARS-CoV-2 spike protein receptor binding domain (sRBD) on the spore surface was developed. In a pilot test, no adverse health event was observed in either mice or healthy human volunteers after three oral courses of B. subtilis spores. Significant increases in neutralizing antibody against sRBD, in both mice and human volunteers, after oral administration were also found. These findings may enable the further clinical developments of B. subtilis spores as an oral vaccine candidate against COVID-19 in the future.