Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes
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Updated: Feb 18, 2026
Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Marley C Caballero Van Dyke1,2, Ashok K Chaturvedi1,2, Sarah E Hardison1,2
1Department of Biology, The University of Texas at San Antonio, San Antonio, TX, United States.
Abstract:
Cryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neoformans serotype A strain engineered to produce interferon-γ, denoted H99γ, are protected against a subsequent otherwise lethal experimental infection with C. neoformans serotype A. Thus, we determined the efficacy of immunization with C. neoformans strain H99γ to elicit broad-spectrum protection in BALB/c mice against multiple disparate Cryptococcus serotypes. We observed significantly increased survival rates and significantly decreased pulmonary fungal burden in H99γ immunized mice challenged with Cryptococcus serotypes A, B, or D compared to heat-killed H99γ (HKH99γ) immunized mice. Results indicated that prolonged protection against Cryptococcus serotypes B or D in H99γ immunized mice was CD4+ T cell dependent and associated with the induction of predominantly Th1-type cytokine responses. Interestingly, immunization with H99γ did not elicit greater protection against challenge with the Cryptococcus serotype C tested either due to low overall virulence of this strain or enhanced capacity of this strain to evade host immunity. Altogether, these studies provide "proof-of-concept" for the development of a cryptococcal vaccine that provides cross-protection against multiple disparate serotypes of Cryptococcus.
Insights
An experimental vaccine using a modified Cryptococcus neoformans strain (H99γ) shows promise for preventing cryptococcosis. This H99γ vaccine demonstrated broad-spectrum protection against multiple Cryptococcus serotypes in mice, offering a potential new strategy for fungal disease prevention.
Area of Science:
- Mycology and Immunology
- Infectious Diseases
- Vaccine Development
Background:
- Cryptococcosis is a serious fungal infection caused by various *Cryptococcus* serotypes, with no current vaccine available.
- Previous studies showed a modified *Cryptococcus neoformans* strain (H99γ) protected mice against homologous *C. neoformans* serotype A infection.
Purpose of the Study:
- To evaluate the efficacy of H99γ immunization in providing broad-spectrum protection against multiple *Cryptococcus* serotypes.
- To investigate the immunological mechanisms underlying H99γ-induced protection.
Main Methods:
- BALB/c mice were immunized with *C. neoformans* strain H99γ or heat-killed H99γ (HKH99γ).
- Mice were subsequently challenged with different *Cryptococcus* serotypes (A, B, C, D).
- Survival rates, pulmonary fungal burden, and T cell responses (including cytokine profiles) were assessed.
Main Results:
- H99γ immunization significantly increased survival and reduced fungal burden in mice challenged with *Cryptococcus* serotypes A, B, and D, compared to HKH99γ.
- Protection against serotypes B and D was dependent on CD4+ T cells and associated with Th1 cytokine responses.
- H99γ did not provide enhanced protection against *Cryptococcus* serotype C, possibly due to the strain's low virulence or immune evasion capabilities.
Conclusions:
- H99γ immunization offers a proof-of-concept for a cryptococcal vaccine providing cross-protection against multiple *Cryptococcus* serotypes.
- The findings highlight the potential of engineered fungal vaccines for combating cryptococcosis.
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