Abstract
Malaria remains a widespread public health problem in tropical and subtropical regions around the world, and there is still no vaccine available for full protection. In recent years, it has been observed that spores of Bacillus subtillis can act as a vaccine carrier and adjuvant, promoting an elevated humoral response after co-administration with antigens either coupled or integrated to their surface. In our study, B. subtillis spores from the KO7 strain were used to couple the recombinant CSP protein of P. falciparum (rPfCSP), and the nasal humoral-induced immune response in Balb/C mice was evaluated. Our results demonstrate that the spores coupled to rPfCSP increase the immunogenicity of the antigen, which induces high levels of serum IgG, and with balanced Th1/Th2 immune response, being detected antibodies in serum samples for 250 days. Therefore, the use of B. subtilis spores appears to be promising for use as an adjuvant in a vaccine formulation.
Highlights
Immunoblot using anti-6xHIS tag and anti-PfCSP monoclonal antibodies (Lane 2, Fig. 1D, Supplementary figure 2B,C) recognized rPfCSP in the apparent molecular mass and in higher-mass proteins, confirming that all of them correspond to the designed recombinant PfCSP
Predictions made via statistical analysis demonstrated that the rPfCSP + SBsKO7 and rPfCSP groups presented anti-rPFCSP at the same level of negative control on D262 and D243, respectively. These results indicate that the rPfCSP delivered through B. subtilis spores induces the production of longer-lasting antibodies
The results observed in this study demonstrated the improvement in the production of cytophilic antibodies after the use of B. subtilis spores as an adjuvant and antigen carrier
Summary
After the integration of antigens in the surface of spores by coupling or recombination, it was observed that they act as adjuvants in different routes of administration, and stimulate the production of pro-inflammatory cytokines and the recruitment/maturation of dendritic cells[11,12,13]. These spores can induce high levels of IgA and IgG neutralizing antibodies and amplify the cellular response of T C D4+/CD8+ antigen-specific cells[14,15]. The recombinant PfCSP (rPfCSP) production and the analysis of the humoral response (total IgG and subclasses) of the immunized animals against this antigen are described
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