Viable spores of Coccidioides posadasii Δcps1 are required for vaccination and provide long lasting immunity

Abstract

Coccidioidomycosis is a systemic fungal infection for which a vaccine has been sought for over fifty years. The avirulent Coccidioides posadasii strain, Δcps1, which is missing a 6 kb gene, showed significant protection in mice. These studies explore conditions of protection in mice and elucidate the immune response. Mice were vaccinated with different doses and viability states of Δcps1 spores, challenged with virulent C. posadasii, and sacrificed at various endpoints, dependent on experimental objectives. Tissues from vaccinated mice were harvested for in vitro elucidation of immune response. Vaccination with viable Δcps1 spores was required for protection from lethal challenge. Viable spore vaccination produced durable immunity, lasting at least 6 months, and prolonged survival (≥6 months). The C. posadasii vaccine strain also protected mice against C. immitis (survival ≥ 6 months). Cytokines from infected lungs of vaccinated mice in the first four days after Cp challenge showed significant increases of IFN-γ, as did stimulated CD4⁺ spleen cells from vaccinated mice. Transfer of CD4⁺ cells, but not CD8⁺ or B cells, reduced fungal burdens following challenge. IFN-γ from CD4⁺ cells in vaccinated mice indicates a Th1 response, which is critical for host control of coccidioidomycosis.

Keywords: Coccidioides; IFN-γ; Mice; Vaccine; Δcps1.