Our research on pathogenesis of disseminated
candidiasis led to the discovery that
antibodies specific for Candida albicans cell surface β-1, 2-mannotriose [β-(Man)(3)] protect mice. A 14 mer
peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/
cell surface protein fructose-bisphosphate aldolase, was used as the
glycan carrier and resulted in a novel synthetic
glycopeptide vaccine β-(Man)(3)-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the
glycan and
peptide parts of the
vaccine. In this report, we modified the β-(Man)(3)-Fba conjugate by coupling it to
tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)(3)-Fba-TT was administered either alone or as a mixture made with
alum or
monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS
buffer prior to challenge. To confirm that induced
antibodies were protective, sera from mice immunized against the β-(Man)(3)-Fba-TT conjugate transferred protection against disseminated
candidiasis to naïve mice, whereas C. albicans-absorbed
immune sera did not. Similar antibody responses and protection induced by the β-(Man)(3)-Fba-TT
vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the
glycopeptide conjugate results in a self-adjuvanting
vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a major step forward in
vaccine design against disseminated
candidiasis.