Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice
Cryptococcus gattii, a resurging fungal pathogen, poses a major threat in immunocompetent hosts and can cause fatal infection in the pulmonary and central nervous systems. C. gattii received significant attention after the outbreak on Vancouver Island, Canada, which spread further southward to the Pacific Northwest of the United States. Our goal in this project is to identify cryptococcal proteins that may serve in a subunit vaccine which could be used to prevent C. gattii infection. Mice immunized with the cryptococcal proteins of C. gattii showed a reduced pulmonary fungal burden and a prolonged survival following the receipt of an experimental pulmonary infection with C. gattii. Our survival study showed a median survival rate of 60 days in immunized mice compared to only 35 days in mock immunized mice. A Th1/IL-17 cytokine response with the release of chemokines was elicited during the anamnestic immune response against C. gattii. Immunized mice also showed increased C. gattii-specific antibodies in the sera including IgG1, IgG2a, IgA and IgM following infection. Based on these results, immunoblot analysis predicted the presence of many immunodominant protein bands. In conclusion, identifying the protein which would elicit both a B-cell and a T-cell response would be a step closer for an ideal vaccine candidate.
Keywords: Cryptococcus gattii, Th1/IL-17 cytokine response and vaccine.