INDUCTION OF PROTECTIVE IMMUNITY AGAINST CRYPTOCOCCOSIS CAUSED BY DISPARATE CRYPTOCOCCUS SEROTYPES
Marley Van Dyke, Ashok Chaturvedi, Chrissy Leopold Wager, Camaron Hole, Karen Wozniak, Floyd Wormley.
The University of Texas at San Antonio, San Antonio, TX.
Cryptococcosis is a fungal disease caused by Cryptococcus neoformans (serotypes A and D) or Cryptococcus gattii (serotypes B and C). Cryptococcus causes pulmonary infections and can lead to life-threatening infections of the central nervous system. We have shown that mice given an experimental pulmonary inoculation with an IFN-γ producing C. neoformans serotype A strain, designated H99γ, resolve the acute infection and are protected against a subsequent pulmonary challenge with fully pathogenic serotype A strain. However, no study has shown that cross-protection against disparate Cryptococcus serotypes can be achieved. Consequently, we sought to determine the efficacy of immunization with C. neoformans strain H99γ to elicit protection against all serotypes of Cryptococcus. For these studies, we immunized BALB/c mice with either heat killed H99γ (HKγ) or H99γ and 70 days later challenged these mice with Cryptococcus serotype A-D clinical isolates. The mice were monitored for survival or sacrificed at day 7 and day 14 post-challenge to determine pulmonary fungal burden, leukocyte infiltration, and cytokines/chemokine responses. We observed a significant increase in the survival rates of mice immunized with H99γ compared to mice immunized with HKγ following challenge with serotypes A, B, and D. Additionally, the results showed significantly decreased pulmonary fungal burden, a trending Th1-type cytokine profile, and delayed T cell-mediated immune responses with serotypes B-D compared to those challenged with serotype A in H99γ-immunized mice compared to those immunized with HKγ. These studies provide proof-of-concept for development of a cryptococcal vaccine that induces protection across all Cryptococcus serotypes.