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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Duncan, Rory A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital (New Orleans)
New Orleans
United States
Zip Code
Cartmell, Jonathan; Paszkiewicz, Eugenia; Dziadek, Sebastian et al. (2015) Synthesis of antifungal vaccines by conjugation of ?-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid. Carbohydr Res 403:123-34
Xin, Hong; Dziadek, Sebastian; Bundle, David R et al. (2008) Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce protection against candidiasis. Proc Natl Acad Sci U S A 105:13526-31
Xin, Hong; Cutler, Jim E (2006) Hybridoma passage in vitro may result in reduced ability of antimannan antibody to protect against disseminated candidiasis. Infect Immun 74:4310-21
Cutler, J E (2005) Defining criteria for anti-mannan antibodies to protect against candidiasis. Curr Mol Med 5:383-92
Mochon, A Brian; Cutler, Jim E (2005) Is a vaccine needed against Candida albicans? Med Mycol 43:97-115
Granger, Bruce L; Flenniken, Michelle L; Davis, Dana A et al. (2005) Yeast wall protein 1 of Candida albicans. Microbiology 151:1631-44
Wang, Ping; Cutler, Jim; King, Jill et al. (2004) Mutation of the regulator of G protein signaling Crg1 increases virulence in Cryptococcus neoformans. Eukaryot Cell 3:1028-35
Montagnoli, Claudia; Bozza, Silvia; Bacci, Angela et al. (2003) A role for antibodies in the generation of memory antifungal immunity. Eur J Immunol 33:1193-204
Kruppa, Michael; Goins, Tresa; Cutler, Jim E et al. (2003) The role of the Candida albicans histidine kinase [CHK1) gene in the regulation of cell wall mannan and glucan biosynthesis. FEMS Yeast Res 3:289-99
Sundstrom, Paula; Cutler, Jim E; Staab, Janet F (2002) Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida albicans strains with selectable marker URA3 targeted to the ENO1 locus. Infect Immun 70:3281-3

Showing the most recent 10 out of 46 publications