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Infection and Immunity, October 2006, p. 5802-5813, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00961-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Multivalent Recombinant Protein Vaccine against Coccidioidomycosis

Eric J. Tarcha,1 Venkatesha Basrur,1 Chiung-Yu Hung,2 Malcolm J. Gardner,3 and Garry T. Cole2*

Department of Medical Microbiology and Immunology, Medical University of Ohio, Toledo, Ohio 43614,1 Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, Texas 78249,2 Seattle Biomedical Research Institute, Seattle, Washington 981093

Received 15 June 2006/ Returned for modification 1 July 2006/ Accepted 15 July 2006

Coccidioidomycosis is a human respiratory disease that is endemic to the southwestern United States and is caused by inhalation of the spores of a desert soilborne fungus. Efforts to develop a vaccine against this disease have focused on identification of T-cell-reactive antigens derived from the parasitic cell wall which can stimulate protective immunity against Coccidioides posadasii infection in mice. We previously described a productive immunoproteomic/bioinformatic approach to the discovery of vaccine candidates which makes use of the translated genome of C. posadasii and a computer-based method of scanning deduced sequences of seroreactive proteins for epitopes that are predicted to bind to human major histocompatibility (MHC) class II-restricted molecules. In this study we identified a set of putative cell wall proteins predicted to contain multiple, promiscuous MHC II binding epitopes. Three of these were expressed by Escherichia coli, combined in a vaccine, and tested for protective efficacy in C57BL/6 mice. Approximately 90% of the mice survived beyond 90 days after intranasal challenge, and the majority cleared the pathogen. We suggest that the multicomponent vaccine stimulates a broader range of T-cell clones than the single recombinant protein vaccines and thereby may be capable of inducing protection in an immunologically heterogeneous human population.

* 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.

Editor: A. Casadevall

Infection and Immunity, October 2006, p. 5802-5813, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00961-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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