Evaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosis

dc.contributor.authorHerr, Roger A.
dc.contributor.authorHung, Chiung-Yu
dc.contributor.authorCole, Garry T.
dc.creator.orcidhttps://orcid.org/0000-0003-1091-3420en_US
dc.date.accessioned2023-06-28T15:05:35Z
dc.date.available2023-06-28T15:05:35Z
dc.date.issued2007-12-01
dc.description.abstractEvaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential vaccines against this respiratory disease. A recombinant proline-rich antigen (rAg2/Pra) has been reported to be a leading vaccine candidate. However, contradictory results exist on the protection afforded by this antigen. Subcutaneous vaccination of either C57BL/6 or BALB/c mice with rAg2/Pra plus adjuvant followed by intraperitoneal challenge with C. posadasii resulted in a significant reduction of the fungal burden at 12 to 14 days postchallenge compared to that in nonvaccinated animals. Use of the same vaccination protocol followed by intranasal (i.n.) challenge of C57BL/6 mice with an equal number of organisms culminated in chronic pulmonary infection or death over a 90-day period. Early studies of Ag2/Pra suggested that it is a component of an immunogenic complex. We reveal in this study that C. posadasii produces a homolog of the reported proline-rich antigen, designated Prp2, which shows 69% protein sequence identity and 86% similarity to Ag2/Pra. Protection against i.n. challenge of C57BL/6 mice was evaluated by vaccination with the single bacterially expressed homolog, rAg2/Pra, or rPrp2 in combination with rAg2/Pra, each in the presence of the same adjuvant. The combined vaccine provided significantly better protection than either of the single recombinant protein vaccines. Results of enzyme-linked immunospot assays of the immunized mice revealed that the two proline-rich homologs contain unique T-cell epitopes. In combination, the recombinant proteins stimulate a more heterogeneous and protective T-cell repertoire than the monovalent vaccines.en_US
dc.description.departmentMolecular Microbiology and Immunologyen_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; Margaret Batts Tobin Foundation, San Antonio, TXen_US
dc.identifier.citationHerr, R. A., Hung, C.-Y., & Cole, G. T. (2007). Evaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosis. Infection and Immunity, 75(12), 5777-5787. doi:10.1128/iai.00807-07en_US
dc.identifier.issn1098-5522
dc.identifier.otherhttps://doi.org/10.1128/iai.00807-07
dc.identifier.urihttps://hdl.handle.net/20.500.12588/1950
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofseriesInfection and Immunity;Vol. 75, No. 12
dc.subjectCoccidioides posadasiien_US
dc.subjectCoccidioidesen_US
dc.subjectcoccidioidomycosisen_US
dc.subjectvaccineen_US
dc.titleEvaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosisen_US
dc.typeArticleen_US

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