Methodology for Anti-Cryptococcal Vaccine Development

Cryptococcus neoformans and Cryptococcus gattii, the predominant etiological agents of cryptococcosis, are fungal pathogens that cause disease ranging from a mild pneumonia to life-threatening infections of the central nervous system (CNS). C. neoformans is widely considered an opportunistic fungal pathogen which targets individuals with impaired immune systems, while C. gattii is predominantly associated with fungal infections in immunocompetent individuals. However, C. neoformans and C. gattii have certainly been identified as the causative agent of cryptococcosis in both immune compromised and immune competent individuals. Cell-mediated immunity (CMI) by T-helper (Th) 1-type CD4+ T cells is the predominant host defense mechanism against cryptococcosis. Consequently, there has been great interest in identifying cryptococcal antigens that elicit protective CMI against Cryptococcus infection. Although many different cryptococcal proteins have been shown to stimulate potent cellular responses, there remains no standardized vaccine available for the prevention of cryptococcal infections in humans. Several studies have identified immunodominant antigens that may serve as attractive candidates for the development of novel subunit vaccines for the treatment and/or the prevention of cryptococcosis. The purpose of this chapter is to describe one methodology to screen and isolate cryptocococcal proteins that induce protective immune responses against cryptococossis.