Development of a Bacillus subtilis-based rotavirus vaccine

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Rotavirus is a leading cause of severe diarrheal disease in infants worldwide.
• Development of effective and safe rotavirus vaccines is a global health priority.
• Bacillus subtilis spore-based vaccines offer potential for oral and intranasal delivery, enhancing mucosal immunity.

Purpose of the Study:

• To evaluate the immunogenicity and protective efficacy of Bacillus subtilis spore-based vaccines expressing rotavirus VP6 antigens.
• To assess the role of adjuvants, cholera toxin (CT) and a mutant E. coli heat-labile toxin (mLT), in enhancing vaccine responses.
• To determine the effectiveness of intranasal vaccination against rotavirus challenge in a murine model.

Main Methods:

• Recombinant Bacillus subtilis strains engineered to express bovine or murine rotavirus VP6 were used.
• Adult mice were inoculated intranasally with B. subtilis spores or vegetative cells, with or without CT or mLT adjuvants.
• Vaccine efficacy was assessed by challenging immunized mice with EDIM EW murine rotavirus and monitoring for fecal virus shedding.
• Serum and fecal antibody responses (IgG and IgA) were measured using enzyme-linked immunosorbent assay (ELISA).

Main Results:

• Both VP6 spore and vegetative cell vaccines induced serum anti-VP6 IgG responses.
• Only VP6 spore vaccines generated fecal anti-VP6 IgA responses.
• Mice immunized with VP6 spore vaccines plus CT or mLT showed significantly reduced rotavirus shedding.
• VP6 vegetative cell vaccines did not confer protection against rotavirus challenge.

Conclusions:

• Intranasal administration of Bacillus subtilis spore-based rotavirus vaccines effectively induces protective immunity in mice.
• Spore-based vaccines are superior to vegetative cell-based vaccines for inducing mucosal immunity and protection.
• The combination of B. subtilis spore vaccines with CT or mLT adjuvants enhances protection against rotavirus infection.