Stable episomal expression system under control of a stress inducible promoter enhances the immunogenicity of Bacillus subtilis as a vector for antigen delivery

Vaccine
Juliano D PaccezLuis C S Ferreira

Abstract

Bacillus subtilis has been successfully engineered to express heterologous antigens genetically fused to surface-exposed spore coat proteins as a vaccine vehicle endowed with remarkable heat resistance and probiotic effects for both humans and animals. Nonetheless, the immunogenicity of passenger antigens expressed by B. subtilis spores is low particularly following oral delivery. In this work, we describe a new episomal expression system promoting enhanced immunogenicity of heterologous antigens carried by B. subtilis strains, either in the form of spores or vegetative cells, following oral or parenteral delivery to mice. Based on a bi-directional replicating multicopy plasmid, the gene encoding the B subunit of the heat-labile toxin (LTB), produced by enterotoxigenic Escherichia coli (ETEC) strains, was cloned under the control of the B. subtilis glucose starvation inducible (gsiB) gene promoter, active in vegetative cells submitted to heat and other stress conditions. The recombinant plasmid proved to be structurally and segregationally stable in both cells and spores under in vitro and in vivo conditions. Moreover, BALB/c mice orally immunized with B. subtilis cells or spores elicited enhanced anti-LTB systemic (serum IgG) ...Continue Reading

Citations

Mar 31, 2015·Vaccine·Luana R M M ApsLuís C S Ferreira
Jan 15, 2014·Infection and Immunity·Milene Tavares BatistaLuís C S Ferreira
Sep 12, 2018·World Journal of Microbiology & Biotechnology·Wenjing CuiZhemin Zhou
Jan 20, 2007·Molecular Pharmaceutics·Saba Parsa, Blaine Pfeifer

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