Evaluation of the proline-rich antigen of Coccidioides immitis as a vaccine candidate in mice.
We have expressed the proline-rich antigen (PRA) from Coccidioides immitis in Escherichia coli and evaluated its potential as a vaccine candidate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the recombinant protein (rPRA) revealed two bands, which exhibited virtually identical primary amino acid sequences. T cells from rPRA-immunized BALB/c mice showed a significant in vitro proliferative response to rPRA. A small but statistically significant proliferative response was also induced by rPRA in T cells from mice immunized with whole-cell coccidioidal vaccines. BALB/c mice immunized with rPRA and challenged intraperitoneally with virulent C. immitis had a greatly reduced fungal burden in their lungs and spleens compared to unvaccinated mice. The number of organisms in the lungs was reduced 500-fold, and similar reductions were observed in the spleens of immunized mice. These studies support the continued development of rPRA as a candidate vaccine for prevention of coccidioidomycosis.
VA San Diego HealthCare System and Departments of Pathology and Medicine, University of California, San Diego, California 92161, USA. tkirkland@ucsd.edu
T N
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Kirkland
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Finley
K I
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Orsborn
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Galgiani
D000818:Animals; D000946:Antigens, Fungal / Q000235:genetics / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D003047:Coccidioidomycosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004341:Drug Evaluation; D005260:Female; D005656:Fungal Proteins; D005657:Fungal Vaccines / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011392:Proline / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000946:Antigens, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; D006023:Glycoproteins; D014614:Vaccines, Synthetic; C102758:antigen 2, Coccidioides; D011392:Proline