| Aspergillus fumigatus and other pathogenic fungi cause several thousand deaths per year. Fungal infections occur mainly in immunosuppressed patients who received transplants but can also occur in other patients such as burn victims, premature infants, AIDS patients, people with allergic reactions, and patients in intensive care settings. Aspergillus and Candida species cause the greatest number of fungal infections in immunocompromised patients, but others such as Coccidioides, Mucor, and Cryptococcus have also become important pathogens.;Protein based vaccines are considered promising for the prevention of fungal infection. We investigated the proteomes of thirteen species of fungi via quantitative MSE mass spectrometry, including Aspergillus species, Candida species, Coccidioides posadasii, Mucor circinelloides, Cryptococcus neoformans, and Saccharomyces cerevisiae. Fungal proteins may become candidates for broad spectrum antifungal vaccines, and several identified proteins in our proteome fractions were particularly promising due to their cell surface localization, abundance, low similarity to mammalian proteins, and high expression rates of homologs in several species of fungi. Among the 42 most abundant secreted or cell surface A. fumigatus proteins with homologues in other fungi, only 8 had human homologues, averaging 26% sequence identity. These included several glucanosyltransferases (Bgt1, Gel1-4), Crf1, Ecm33, EglC, and others. Vaccines with recombinant cell wall proteins Sxa2, Alp2, or Bys1 protected against A. fumigatus in a mouse model with corticosteroid immunosuppression. ELISPOT assays revealed that A. fumigatus antigens induce Th1 IFN-gamma production in mouse splenocytes and that antigens separated on polyacrylamide gels reproduce this response. A multi-epitope protein vaccine candidate, MulV1, was developed by concatenating predicted peptide epitope sequences with flanking cathepsin cut sites to enhance immune processing. In summary, we identified several cell wall proteins that may be utilized in the development of broad spectrum antifungal vaccines. |
