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

Publication date: Jun 26, 2023

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.

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Concepts Keywords
Astragalus Bacillus subtilis
Harmless Coriolus versicolor (CV)
Mucosal cytokines
Recombinant dendritic cells
Vaccine macrophages


Type Source Name
disease VO vaccine
disease MESH Infection
disease VO vaccination
disease VO effective
disease MESH COVID-19
disease MESH fear of needles
disease IDO commensal
disease IDO production
disease IDO host
drug DRUGBANK Trametes versicolor fruiting body
disease VO COVID-19 vaccine
disease VO CoronaVac
disease VO dose
drug DRUGBANK Troleandomycin
drug DRUGBANK Coenzyme M
disease IDO infectivity
disease IDO immune response
disease VO oral vaccination
disease MESH infectious diseases
disease VO immunization
drug DRUGBANK keyhole limpet hemocyanin
disease IDO blood
disease IDO assay
disease VO Tox
disease MESH hair loss
drug DRUGBANK Water
disease VO titer
drug DRUGBANK Azelaic acid
disease MESH Inflammation
disease MESH hemorrhage
disease VO vaccinated
drug DRUGBANK Esomeprazole
disease IDO pathogen
disease IDO cell
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease VO vaccine strain
drug DRUGBANK BCG vaccine
disease MESH severe combined immunodeficiency
disease IDO process
drug DRUGBANK Cycloserine
disease MESH viral diseases
disease MESH reinfection
disease VO injection
disease MESH malnutrition
drug DRUGBANK Chloramphenicol
drug DRUGBANK Isopropyl beta-D-thiogalactopyranoside
drug DRUGBANK Phosphate ion
disease VO volume
drug DRUGBANK Potassium Chloride
drug DRUGBANK Magnesium sulfate
drug DRUGBANK Lysozyme
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Phenol
disease IDO endotoxin
drug DRUGBANK Sulfate ion
drug DRUGBANK Dimethyl sulfoxide
disease VO USA
drug DRUGBANK L-Glutamine
drug DRUGBANK Streptomycin
disease IDO colony
drug DRUGBANK Formaldehyde
disease VO inactivated vaccine
disease VO immunized
drug DRUGBANK Tromethamine
drug DRUGBANK Angiotensin II

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