A role of B-cells and antibodies in generation of protective immune responses against a vaccinating antigen during non-albicans Candida mediated systemic candidiasis

Abstract

Abstract While cellular immunity is acknowledged to be critical for vaccine-mediated protection during systemic candidiasis, the role of humoral immunity is not clear. We investigated the role of B cells and antibodies in conferring protective advantage during Candida tropicalis mediated murine systemic candidiasis, using a lead vaccine candidate, Sap2 (secreted aspartyl proteinase 2) obtained from C. parapsilosis. Compared to sham-immunized mice, Sap2-parapsilosis vaccinated mice exhibited significantly improved survival outcomes (p=0.02) and reduced organ fungal burdens (p<0.05). Sap2-parapsilosis vaccination induced high titres of Sap2-specific antibodies, and a fraction of antibodies could bind whole fungus (of predominantly IgM isotype). Notably, sera from Sap2-parapsilosis-vaccinated mice exhibited increased C. tropicalis biofilm inhibition ability and enhanced neutrophil-mediated fungal killing in vitro. Sap2-specificity was further confirmed by depleting antigen-specific antibodies. Passive transfer of Sap2-parapsilosis immune serum significantly reduced fungal burdens in naive mice, as compared to mice receiving sham-immune serum, upon infection. Higher numbers of total CD19+ B cells, plasma cells and Candida-binding B cells in Sap2-vaccinated mice indicate towards a role of B cells during early stages of Sap2-mediated immune response. Epitope analysis performed using identified B cell epitopes provides insights about including important IgM and IgG epitopes, when designing multivalent or multiepitope anti-Candida vaccine/s. In summary, our results establishes a role of B cells and antibodies in contributing towards protective efficacy of Sap2 vaccine antigen during murine systemic candidiasis.