Protection against experimental cryptococcosis elicited by Cationic Adjuvant Formulation 01-adjuvanted subunit...

Area of Science:

• Mycology
• Immunology
• Vaccinology

Background:

• Cryptococcosis, a fungal infection, causes over 100,000 deaths annually, with no licensed vaccines available.
• Subunit vaccines offer a potential strategy to prevent cryptococcosis, but require effective adjuvants to elicit robust immune responses.

Purpose of the Study:

• To evaluate the efficacy and immunogenicity of novel subunit vaccines against cryptococcosis.
• To assess the role of Cationic Adjuvant Formulation 01 (CAF01) in enhancing vaccine-induced immune responses.

Main Methods:

• Mice were vaccinated subcutaneously with single, bivalent, or quadrivalent recombinant Cryptococcus neoformans protein antigens adjuvanted with CAF01.
• Vaccine efficacy was assessed by pulmonary challenge with C. neoformans.
• Immune responses, including T cell populations (CD4+ and CD8+) and cytokine production (IFNγ, TNFα, IL-17), were analyzed in lung tissue, spleen, and blood.

Main Results:

• Single-antigen vaccines provided partial protection, while bivalent and quadrivalent formulations achieved up to 100% protection in mice.
• Vaccinated mice exhibited increased leukocyte influx in the lungs, including polyfunctional CD4+ T cells producing IFNγ, TNFα, and IL-17.
• A significant and durable IFNγ response was observed across multiple tissues, correlating directly with fungal control.

Conclusions:

• Multivalent subunit vaccines formulated with CAF01 are effective in protecting against experimental cryptococcosis in mice.
• The adjuvant CAF01 promotes Th1 and Th17 immune responses crucial for fungal control.
• These findings support the advancement of these cryptococcal vaccines into human clinical trials.