Abstract

Candida albicans is an opportunistic pathogen that causes a diverse array of mucosal and deep tissue infections. The overall goal of this project is to develop an anti-Candida vaccine. The goal of this subproject is to identify Candida albicans gene products that are the best targets against which to develop vaccines. Our strategy and rationale are as follows: 1. We will identify Candida albicans genes that are expressed during infection, based upon screening of random gene fusions. Comparison of junction sequences to the Candida albicans genomic sequence will permit identification of likely secreted, cell wall, and transmembrane proteins, which should be available for interaction with immunoglubulins. Genes that specific such proteins constitutes out set of vaccine target candidate (VTC) genes 2 Epitope-tagging and immunofluorescence analysis will be used to verify expression and surface localization of each VTC gene product. 3. The potential of an anti-VTC immune response to protect against infection will be assessed in anti-epitope reconstruction experiments. Mice immunized with a peptide epitope will be challenged with Candida albicans strains that express individual epitope-tagged VTC gene products, and outcome of infection will be determined by host viability and tissue burden.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI037194-08
Application #
6583726
Study Section
Project Start
2002-04-01
Project End
2003-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
8
Fiscal Year
2002
Total Cost
$196,218
Indirect Cost

  Institution

Name
La Biomed Research Institute/ Harbor UCLA Medical Center
Department
Type
DUNS #
City
Torrance
State
CA
Country
United States
Zip Code
90502

  Publications

Boxx, Gayle M; Kozel, Thomas R; Nishiya, Casey T et al. (2010) Influence of mannan and glucan on complement activation and C3 binding by Candida albicans. Infect Immun 78:1250-9
Boxx, Gayle M; Nishiya, Casey T; Kozel, Thomas R et al. (2009) Characteristics of Fc-independent human antimannan antibody-mediated alternative pathway initiation of C3 deposition to Candida albicans. Mol Immunol 46:473-80
Zhang, Mason X; Bohlman, M Charlotte; Itatani, Carol et al. (2006) Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice. Infect Immun 74:362-9
Lillegard, Joseph B; Sim, Robert B; Thorkildson, Peter et al. (2006) Recognition of Candida albicans by mannan-binding lectin in vitro and in vivo. J Infect Dis 193:1589-97
Granger, Bruce L; Flenniken, Michelle L; Davis, Dana A et al. (2005) Yeast wall protein 1 of Candida albicans. Microbiology 151:1631-44
Ibrahim, Ashraf S; Spellberg, Brad J; Avenissian, Valentina et al. (2005) Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect Immun 73:999-1005
Spellberg, Brad J; Ibrahim, Ashraf S; Avenissian, Valentina et al. (2005) The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect Immun 73:6191-3
Toenjes, Kurt A; Munsee, Suzanne M; Ibrahim, Ashraf S et al. (2005) Small-molecule inhibitors of the budded-to-hyphal-form transition in the pathogenic yeast Candida albicans. Antimicrob Agents Chemother 49:963-72
Cutler, J E (2005) Defining criteria for anti-mannan antibodies to protect against candidiasis. Curr Mol Med 5:383-92
VandenBerg, Alysia L; Ibrahim, Ashraf S; Edwards Jr, John E et al. (2004) Cdc42p GTPase regulates the budded-to-hyphal-form transition and expression of hypha-specific transcripts in Candida albicans. Eukaryot Cell 3:724-34

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