Coccidioides is a fungal pathogen and causative agent of a human respiratory disease against which no clinical
vaccine exists. In this study we evaluated a novel
vaccine adjuvant referred to as EP67, which is a
peptide agonist of the biologically active C-terminal region of human
complement component C5a. The
EP67 peptide was conjugated to live spores of an
attenuated vaccine strain (ΔT) of Coccidioides posadasii. The non-conjugated ΔT
vaccine provided partial protection to BALB/c mice against
coccidioidomycosis. In this report we compared the protective efficacy of the ΔT-EP67 conjugate to the ΔT
vaccine in BALB/c mice. Animals immunized subcutaneously with the ΔT-EP67
vaccine showed significant increase in survival and decrease in fungal burden over 75 days postchallenge. Increased pulmonary infiltration of dendritic cells and macrophages was observed on day 7 postchallenge but marked decrease in neutrophil numbers had occurred by 11 days. The reduced influx of neutrophils may have contributed to the observed reduction of inflammatory pathology. Mice immunized with the ΔT-EP67
vaccine also revealed enhanced expression of
MHC II molecules on the surface of antigen presenting cells, and in vitro recall assays of immune splenocytes showed elevated Th1- and Th17-type
cytokine production. The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4(+) T cells. Elevated expression of T-bet and RORc
transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation. Higher titers of Coccidioides
antigen-specific
IgG1 and
IgG2a were detected in mice immunized with the EP67-conjugated versus the non-conjugated
vaccine. These combined results suggest that the EP67 adjuvant enhances protective efficacy of the live
vaccine by augmentation of T-cell immunity, especially through Th1- and Th17-mediated responses to
Coccidioides infection.