Vaccine-Mediated Protection of Mice Against African and Asian Clinical Strains of Cryptococcus neoformans.

Infections with strains of the Cryptococcus neoformans species complex are responsible for over 100,000 deaths per year, predominantly due to meningitis in immunocompromised individuals. Despite much research, there are no licensed fungal vaccines available. Most experimental cryptococcal vaccine formulations have been tested in preclinical models using laboratory strains of C. neoformans, particularly H99 and KN99. However, to be effective, vaccines need to protect against the wide variety of cryptococcal isolates found worldwide, particularly in regions that have the highest burden of infections. Therefore, we explored vaccine-mediated protection of BALB/c mice against experimental cryptococcosis due to six C. neoformans strains originally isolated from patients with cryptococcal meningitis in Vietnam, Uganda, and Botswana. Two vaccines were tested: a live-attenuated C. neoformans vaccine lacking three chitin deacetylase genes, and a quadrivalent subunit protein vaccine adjuvanted with Cationic Adjuvant Formulation 01. When compared to unvaccinated mice, both vaccines provided significant protection against all six clinical strains. However, the degree of protection varied as a function of vaccine formulation and clinical strain. Lung leukocytes from vaccinated and infected mice had significantly increased antigen-stimulated interferon-gamma production compared with infected but unvaccinated mice. Thus, although the degree of protection varied, two cryptococcal vaccines significantly protected mice against experimental infection with cryptococcal strains representative of regions of the world that account for the majority of cryptococcal meningitis cases found globally. These data provide preclinical support for trialing vaccines in persons at high risk for developing cryptococcosis.

Duke Scholars

Author Jennifer L Tenor Medicine, Infectious Diseases

Author John Robert Perfect Medicine, Infectious Diseases