Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice

PLoS One. 2014 Aug 13;9(8):e104316. doi: 10.1371/journal.pone.0104316. eCollection 2014.

Abstract

Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intranasal
  • Analysis of Variance
  • Animals
  • Chromatography, High Pressure Liquid
  • Cryptococcosis / immunology*
  • Cryptococcus gattii / immunology*
  • Cytokines / immunology
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Flow Cytometry
  • Fungal Vaccines / administration & dosage
  • Fungal Vaccines / immunology*
  • Immunoblotting
  • Lung Diseases / immunology
  • Lung Diseases / microbiology*
  • Mice
  • Mice, Inbred BALB C
  • Tandem Mass Spectrometry

Substances

  • Cytokines
  • Fungal Vaccines