Immunological correlates of protection following vaccination with glucan particles containing Cryptococcus neoformans chitin deacetylases

Abstract

Vaccination with glucan particles (GP) containing the Cryptococcus neoformans chitin deacetylases Cda1 and Cda2 protect mice against experimental cryptococcosis. Here, immunological correlates of vaccine-mediated protection were explored. Studies comparing knockout and wild-type mice demonstrated CD4+ T cells are crucial, while B cells and CD8+ T cells are dispensable. Protection was abolished following CD4+ T cell depletion during either vaccination or infection, but was retained if CD4+ T cells were only partially depleted. Vaccination elicited systemic and durable antigen-specific immune responses in PBMCs, spleen and lungs. Following vaccination and fungal challenge, robust Th1 and Th17 responses were observed in the lungs. Protection was abrogated in mice congenitally deficient in IFNɣ, IFNɣ receptor, IL-1β, IL-6, or IL-23. Thus, CD4+ T cells and specific pro-inflammatory cytokines are required for GP-vaccine mediated protection. Importantly, retention of protection in the setting of partial CD4+ T depletion suggests a pathway for vaccinating at-risk immunocompromised individuals.