Multivalent Vaccine for Preventing Invasive Candidiasis

Objectives: To adopt a preventive peptide vaccine-based approach against invasive Candida albicans (C. albicans) infection. The multi-epitope vaccine for C. albicans (MVC) was designed by linking the top-ranking epitopes in the entire candida proteome (consisting of 6030 proteins). MVC consists of epitopes for cytotoxic T-cells (Tc), helper T- cells (Th) and B-cells, and therefore has the potential to elicit cell- as well as antibody- based immune response.

Methods: We identified the eight most immunogenic hyphal proteins from the candida proteome using the VaxiJen server. Next, we screened the selected epitopes for HLA class I (using NetCTL), HLA class II (using IEDB) and B- cell (BCPreds) response. Based on conservancy analyses, we selected 18 epitopes showing a 100% conservancy. Further, the epitopes were joined by -AAY- and -GPGPG- linker sequences to form a recombinant protein. We also incorporated a TLR4 agonist RS09 (APPHALS), as an adjuvant at the N- terminal end of the final vaccine construct.

Results: Immunoinformatic analyses provided us with a stable 3D- multi-epitope subunit vaccine for C. albicans (MVC). The selected MVC epitopes are homologous against all currently available annotated reference sequences of 22 C. albicans strains, thus offering a higher coverage and protective response. Characterization of MVC’s biophysiochemical properties, antigenicity and allergenicity showed optimal vaccine characteristics.

Conclusions: The strength of the proposed approach to candida vaccination is its multivalent nature (recognizing multiple-epitopes), as compared to univalent vaccines against a single antigen. The immunogenicity and efficacy of MVC remain to be validated experimentally.