A Multivalent Subunit Vaccine Offers Cross Protection Against Both Species of Coccidioides

Date
2019
Authors
Pentakota, Komali
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Abstract

Valley fever is a life-threatening disease caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci). Currently there is no licensed vaccine for this disease. We have created a recombinant Coccidioides polypeptide antigen (rCpa1) that contains 3 previously identified antigens and 5 short peptides derived from 3 additional proteins of Cp C735 isolate. The purified rCpa1 loaded into glucan-chitin particles (GCPs) as a delivery and adjuvant system offers protection for mice against pulmonary challenge with the autologous isolate. We had sequenced these 6 genes for additional 39 and 17 clinical isolates of Cp and Ci, respectively. Deduced amino acid sequence analysis revealed that these 6 antigens have intraspecies identity. But there are 7 amino acid substitutions between Cp and Ci. Bioinformatics analysis using a ProPed algorithm implicates that these 7 substitutions are not located on the predicted epitope regions. Next, we evaluated protective efficacy of the GCP+rCpa1 vaccine against additional 4 clinical isolates of Cp (isolate 3488 and Silveira) and Ci (isolate RS and 2394). Vaccinated mice had statistically significant reduction in fungal burden against all of the tested Cp and Ci isolates compared to non-vaccinated mice. The degree of protection for these isolates was comparable to Cp C735. Furthermore, significantly elevated numbers of IFN-γ and IL-17-producing CD4+ T helper cells were recruited to the lungs of vaccinated mice against all tested isolates at 7 and 14 days post challenge. These data reveal that a mixed Th1 and Th17 immunity is associated with protection against these 4 isolates. Taken together, these data support our previous observation that Th1 and Th17 response are essential for vaccine immunity against coccidioidomycosis.

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Keywords
Coccidiodomycosis, Coccidioides, Fungal Vaccine, Th1, Th17, Vaccine immunity, Valley Fever
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Department
Integrative Biology