Creating a Vaccine-like Supplement against Respiratory Infection Using Recombinant Bacillus subtilis Spores Expressing SARS-CoV-2 Spike Protein with Natural Products

Abstract

Vaccination is the most effective method of combating COVID-19 infection, but people with a psychological fear of needles and side effects are hesitant to receive the current vaccination, and alternative delivery methods may help. Bacillus subtilis, a harmless intestinal commensal, has recently earned a strong reputation as a vaccine production host and delivery vector, with advantages such as low cost, safety for human consumption, and straightforward oral administration. In this study, we have succeeded generating “S spores” by engineering B. subtilis with spore coat proteins resembling the spike (S) protein of the ancestral SARS-CoV-2 coronavirus. With the addition of two immunostimulating natural products as adjuvants, namely Astragalus membranaceus (Fisch.) Bge (AM) and Coriolus versicolor (CV), oral administration of S spores could elicit mild immune responses against COVID-19 infection without toxicity. Mucosal IgA against the S protein was enhanced by co-feeding with AM and CV in an S spores-inoculated mouse model. Faster and stronger IgG responses against the S protein were observed when the mice were fed with S spores prior to vaccination with the commercial COVID-19 vaccine CoronaVac. In vitro studies demonstrated that AM, CV, and B. subtilis spores could dose-dependently activate both macrophages and dendritic cells by secreting innate immunity-related IL-1β, IL-6, and TNF-α, and some other proinflammatory chemokines and cytokines. In conclusion, the combination of S spores with AM and CV may be helpful in developing a vaccine-like supplement against respiratory infection.

Recent development of oral vaccines (Review)

“…These innovative vaccine vectors offer unique advantages, such as their inherent immunogenicity and ability to traverse the gastrointestinal tract unharmed ( 53 ). B. subtilis , a versatile bacterium, can deliver antigens effectively and stimulate both the mucosal and systemic immune responses ( 167 ). Yeast-based vaccine platforms have also demonstrated their potential in inducing strong humoral and cellular immune responses ( 168 ).…”

Applications of Bacillus subtilis Protein Display for Medicine, Catalysis, Environmental Remediation, and Protein Engineering

“…In another investigation, the spike protein of the ancestorial SARS-CoV-2 coronavirus was fused to CotC. This fusion with additional adjuvants demonstrated activation of macrophages and dendritic cells [ 17 ].…”