Abstract
Bacillus subtilis spores have received growing attention regarding potential biotechnological applications, including the use as probiotics and in vaccine formulations. B. subtilis spores have also been shown to behave as particulate vaccine adjuvants, promoting the increase of antibody responses after co-administration with antigens either admixed or adsorbed on the spore surface. In this study, we further evaluated the immune modulatory properties of B. subtilis spores using a recombinant HIV gag p24 protein as a model antigen. The adjuvant effects of B. subtilis spores were not affected by the genetic background of the mouse lineage and did not induce significant inflammatory or deleterious effects after parenteral administration. Our results demonstrated that co-administration, but not adsorption to the spore surface, enhanced the immunogenicity of that target antigen after subcutaneous administration to BALB/c and C57BL/6 mice. Spores promoted activation of antigen presenting cells as demonstrated by the upregulation of MHC and CD40 molecules and enhanced secretion of pro-inflammatory cytokines by murine dendritic cells. In addition, in vivo studies indicated a direct role of the innate immunity on the immunomodulatory properties of B. subtilis spores, as demonstrated by the lack of adjuvant effects on MyD88 and TLR2 knockout mouse strains.
Highlights
Adjuvants are compounds that enhance the potency, quality or longevity of specific immune responses
B. subtilis spores have been used as particulate adjuvants for enhancing immune responses based in two main approaches: coadministration with soluble antigens or with proteins adsorbed onto the spore surface [7,8]
To verify which strategy would confer stronger adjuvant effects, we used the recombinant HIV-1 gag p24 protein, which has been used in several anti-HIV vaccine strategies as a model antigen [23,24,28]
Summary
Adjuvants are compounds that enhance the potency, quality or longevity of specific immune responses. Adjuvants can be classified as delivery systems, immunopotentiators or a combination of both Delivery systems, such as mineral salts, emulsions and liposomes, efficiently present the antigens to the immune system by aggregating and controlling antigen release. Immunopotentiators, such as cytokines, saponins and Toll-like receptor agonists, increase the immune response to antigens by stimulating the innate immune cells directly [3,4,5]. These adjuvants boost immunity by activating antigen-presenting cells (APCs), which increase the expression of MHC I and/or II molecules, cytokines and the co-stimulatory molecules that are required for T-cell contact and activation. APC maturation determines the magnitude and the type of the T and B cell responses [6]
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