Identification and characterization of Cryptococcus neoformans protein fractions that induce protective immune responses

Ashok K. Chaturvedi, Susan E Weintraub, Jose L. Lopez-Ribot, Floyd L. Wormley

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cryptococcus neoformans, the main causative agent of cryptococcosis, is a fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. To date, there is no vaccine or immunotherapy approved to treat cryptococcosis. Cell- and antibody-mediated immune responses collaborate to mediate optimal protection against C. neoformans infections. Accordingly, we identified cryptococcal protein fractions capable of stimulating cell- and antibody-mediated immune responses and determined their efficacy to elicit protection against cryptococcosis. Proteins were extracted from C. neoformans and fractionated based on molecular mass. The fractions were then evaluated by immunoblot analysis for reactivity to serum extracted from protectively immunized mice and in cytokine recall assays for their efficacy to induce pro-inflammatory and Th1-type cytokine responses associated with protection. MS analysis revealed a number of proteins with roles in stress response, signal transduction, carbohydrate metabolism, amino acid synthesis, and protein synthesis. Immunization with select protein fractions containing immunodominant antigens induced significantly prolonged survival against experimental pulmonary cryptococcosis. Our studies support using the combination of immunological and proteomic approaches to identify proteins that elicit antigen-specific antibody and Th1-type cytokine responses. The immunodominant antigens that were discovered represent attractive candidates for the development of novel subunit vaccines for treatment and/or prevention of cryptococcosis.

Original languageEnglish (US)
Pages (from-to)3429-3441
Number of pages13
JournalProteomics
Volume13
Issue number23-24
DOIs
StatePublished - Dec 2013

Fingerprint

Cryptococcus neoformans
Cryptococcosis
Immunodominant Epitopes
Proteins
Cytokines
Antibodies
Immunization
Signal transduction
Subunit Vaccines
Meningoencephalitis
Carbohydrate Metabolism
Immunocompromised Host
Molecular mass
Pathogens
Proteomics
Immunotherapy
Assays
Signal Transduction
Vaccines
Antigens

Keywords

  • Cryptococcosis
  • Cryptococcus neoformans
  • Cytoplasmic proteins
  • Microbiology
  • Surface proteins
  • Vaccination

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Identification and characterization of Cryptococcus neoformans protein fractions that induce protective immune responses. / Chaturvedi, Ashok K.; Weintraub, Susan E; Lopez-Ribot, Jose L.; Wormley, Floyd L.

In: Proteomics, Vol. 13, No. 23-24, 12.2013, p. 3429-3441.

Research output: Contribution to journalArticle

Chaturvedi, Ashok K. ; Weintraub, Susan E ; Lopez-Ribot, Jose L. ; Wormley, Floyd L. / Identification and characterization of Cryptococcus neoformans protein fractions that induce protective immune responses. In: Proteomics. 2013 ; Vol. 13, No. 23-24. pp. 3429-3441.
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