Immune response of vaccinated and non-vaccinated mice to Coccidioides posadasii infection

Abstract

An immunogenic, recombinant protein of the fungal respiratory pathogen, Coccidioides posadasii, was previously identified as a β-1,3-glucanosyltransferase homolog (Gel1) and shown to confer protection to C57BL/6 mice against coccidioidomycosis. However, little is known about the nature of the humoral and cellular immune responses of these vaccinated mice to intranasal infection with a lethal inoculum of C. posadasii spores compared to non-immune control animals. Our studies showed that protective immunity in mice vaccinated with two 1 μg doses of the recombinant Gel1 (rGel1) plus adjuvant was characterized by high titers of antigen-specific IgG2c and elevated levels of interleukin (IL)-12 and interferon-gamma (IFN-γ) production at 7–14 days post-challenge compared to significantly lower levels of the respective antibody and cytokines in non-immune, infected mice. Mice immunized with either 0.2 or 5 μg doses of rGel1 plus adjuvant were less well protected and showed evidence of a marked decrease in the level of T helper-type 1 (T H1) immune response. Early T H1 immune regulation is essential for protection against pulmonary infection with Coccidioides, and the dose of the rGel1 vaccine narrowly defines the nature of immune response in the lungs of infected mice.