title: Vaccine and monoclonal antibody that enhance mouse resistance to candidiasis.
abstract: Previously we showed that antibodies specific for the glycan β-1,2-mannotriose [β-(Man)(3)] on the cell surface of Candida albicans protect mice against disseminated candidiasis (H. Xin, S. Dziadek, D. R. Bundle, and J. E. Cutler, Proc. Natl. Acad. Sci. U. S. A. 105:13526-13531, 2008). Furthermore, six 14-mer peptides that are within the N-terminal portion of C. albicans wall proteins were conjugated to the glycan in an attempt to create immunogenic glycopeptide conjugates. By a dendritic cell (DC)-based immunization approach, all were immunogenic and three of the six conjugates induced a high degree of protection in mice. Interestingly, whereas all six peptides induced antibody responses when used alone to pulse DCs for subsequent immunizations, three peptides induced protection, and one in particular, peptide Fba (derived from fructose-bisphosphate aldolase), induced robust protective responses and is the focus of the current work. Fba peptide is not restricted by the major histocompatibility complex class II (MHC-II), as it induced anti-Fba antibodies in mice of different H-2 haplotypes and in rabbits. Furthermore, the peptide induced protection against disease caused by different C. albicans strains. Partial protection was achieved when alum was used in place of DCs for Fba immunizations. The passive transfer of immune sera from Fba-vaccinated mice, but not immune serum preabsorbed with fungal cells, conferred protection in naïve mice. This result, along with our finding that a monoclonal antibody specific for the peptide, E2-9 (IgM), protected mice against candidiasis, provide strong evidence that antibodies contribute to protection. Our work demonstrates the utility of cell wall peptides alone or as glycopeptides in vaccines designed for the induction of immunity against candidiasis and monoclonal antibodies as a rapid immunoprotective approach against the disease.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center and Research Institute for Children, Children’s Hospital, New Orleans, Louisiana 70118, USA. hxin@chnola-research.org
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Jim E
authors.initials: JE
authors.lastname: Cutler
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000517:prevention & control* / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D005657:Fungal Vaccines; D018074:Vaccines, Conjugate