CANDIDA ALBICANS SURFACE ANTIGENS
Principal Investigator: J E Cutler
Abstract: Various forms of candidiasis plague our society, but our research over the past few years shows promise of vaccine development and antibody strategies against this opportunistic fungal disease. We have determined, in part, mechanisms of antibody protection against hematogenously disseminated candidiasis, but further studies are necessary to complete our understanding of mechanisms by which the antibodies protect against vaginal infection. We have structurally defined the key minimal oligomannoside epitope against which antibodies protect experimental animals against both hematogenously disseminated and vaginal forms of candidiasis, but a complete definition of the epitope should lead to more ideal vaccine formulations. We know that an oligomannoside without an appropriate protein carrier will not induce a protective antibody response, hence we propose to identify cell wall proteins that may serve a dual role as carrier and inducer of anti-protein protective responses. These studies should also lead to insights into the function of phosphomannoprotein complexes in Candida albicans cell walls. These various investigations will proceed by fulfillment of the following five specific aims: 1. Extend the studies on protective antibody/complement-dependency mechanisms involved in protection against hematogenously disseminated candidiasis by determining whether the entire complement cascade is necessary and whether the antibodies are protective in the absence of normal neutrophil and macrophage functions. 2. Determine whether antibody protection against vaginal infection involves complement. 3. Determine if bispecific antibodies that recognize both the beta-1,2-mannotriose and complement receptor on phagocytes are protective and do not require serum complement for protection. 4. Determine the complete epitope recognized by MAbs B6.1 (IgM) and C3.1 (IgG3). 5. Identify proteins N-linked to the phosphomannan complexes that display the beta-1,2-mannotriose, identify possible conjugate partners (carrier protein) for the phosphomannan vaccine formulation being developed on our P01 project and produce mutants to initiate studies into the function of these proteins.
Funding Period: 1988-03-01 - 2008-04-30
more information: NIH RePORT
- Is a vaccine needed against Candida albicans?A Brian Mochon
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA
Med Mycol 43:97-115. 2005..This review is a discussion of our current understanding of the interplay between commensal and pathogenic forms of Candida albicans and approaches toward active and passive immunoprevention against candidiasis...
- Yeast wall protein 1 of Candida albicansBruce L Granger
Department of Microbiology, Montana State University, Bozeman, MT, USA
Microbiology 151:1631-44. 2005..albicans...
- Defining criteria for anti-mannan antibodies to protect against candidiasisJ E Cutler
The Research Institute for Children and LSUHSC, Dept of Pediatrics and Dept of Microbiology, Children s Hospital, New Orleans, LA 70118, USA
Curr Mol Med 5:383-92. 2005....
- Hybridoma passage in vitro may result in reduced ability of antimannan antibody to protect against disseminated candidiasisHong Xin
Research Institute for Children, Children s Hospital, 200 Henry Clay Ave, New Orleans, LA 70118, USA
Infect Immun 74:4310-21. 2006....
- Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce protection against candidiasisHong Xin
Department of Pediatrics, Louisiana State University Health Sciences Center and Research Institute for Children, Children s Hospital, New Orleans, LA 70118, USA
Proc Natl Acad Sci U S A 105:13526-31. 2008..This approach based on fully synthetic chemically defined immunogens should be generally useful in vaccine development...