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Infection and Immunity, December 2007, p. 5777-5787, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00807-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Roger A. Herr,1,{dagger} Chiung-Yu Hung,2 and Garry T. Cole2*

Department of Medical Microbiology and Immunology, University of Toledo Health Science Campus, Toledo, Ohio 43614,1 Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, Texas 782492

Received 12 June 2007/ Returned for modification 26 July 2007/ Accepted 30 August 2007

Evaluation 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.

* Corresponding author. Mailing address: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0662. Phone: (210) 458-7017. Fax: (210) 458-7015. E-mail: garry.cole{at}utsa.edu

{triangledown} Published ahead of print on 17 September 2007.

Editor: A. Casadevall

{dagger} Present address: Department of Pathology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110.

Infection and Immunity, December 2007, p. 5777-5787, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00807-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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