Utilização de esporos de Bacillus toyonensis como adjuvante de vacina recombinante de subunidade contra Herpesvírus Bovino tipo 5

Abstract

Vaccinal adjuvants are compounds that potentiate the immune response. Bacterial spores of the Bacillus genus are able to enhance the immune response when used in vaccines. The aim of this work was to evaluate the use of Bacillus toyonensis spores as an adjuvant to an experimental vaccine as well as conducting a systematic review of studies that used Bacillus spores as adjuvants to different vaccines tested in animal model. Live and heat-killed Bacillus toyonensis spores were used in a vaccine containing the recombinant glycoprotein D (rgD) of Bovine Herpesvirus type 5 (BoHV-5). Six experimental groups of mice were vaccinated subcutaneously on day 0 and boosted on day 21 of the experiment, with the following vaccine formulations: rgD (40 μg) + live spores (2x109 CFU); rgD + inactivated spores (2 x 109 UFC); rgD + live spores + alum (2 mg); rgD + inactivated spores + alum; rgD + alum and rgD + PBS. Significant levels (p <0.05) of total IgG antibodies were observed up to 7.5 times higher in the group that received live spores associated with rgD and adsorbed to alum and 12 times higher in the group that received inactivated spores associated with rgD and adsorbed to alum, when compared to the rgD + alum (control) group. Significant levels of IgG1 of ~8-fold, IgG2a of ~~16-fold and IgG2b of ~8-fold (p<0.05) were detected in mice that received live or inactivated spores adsorbed to alum in the vaccine formulation, when compared to the rgD + alum group. Groups of animals that received live or inactivated spores adsorbed to alum also presented levels of neutralizing antibodies against BoHV-5 and significant levels of IFN-γ mRNA transcription up to 66-fold, IL17 of 14-fold and IL12 of 2.8-fold (p<0.05), when compared to the rgD + alum group. Studies found in the systematic review also showed that vaccination with formulations containing spores of B. subtilis, B. toyonensis, and B. atrophaeus induced the development of a humoral and cellular immune response in the animals, with significant production of antibodies and expression of cytokines, in addition to stimulation and proliferation of immune cells. In conclusion, our data demonstrated that the Bacillus spores have immunomodulatory properties and are capable of improving the response of vaccines, standing out as promising components to be used as adjuvants in vaccine formulations.