Kirkland T N, Finley F, Orsborn K I, Galgiani J N
VA San Diego HealthCare System and Departments of Pathology and Medicine, University of California, San Diego, California 92161, USA.
Infect Immun. 1998 Aug;66(8):3519-22. doi: 10.1128/IAI.66.8.3519-3522.1998.
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.
我们已在大肠杆菌中表达了来自粗球孢子菌的富含脯氨酸抗原(PRA),并评估了其作为候选疫苗的潜力。重组蛋白(rPRA)的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析显示出两条带,它们的一级氨基酸序列几乎相同。来自rPRA免疫的BALB/c小鼠的T细胞对rPRA表现出显著的体外增殖反应。rPRA在用全细胞球孢子菌疫苗免疫的小鼠的T细胞中也诱导了轻微但具有统计学意义的增殖反应。与未接种疫苗的小鼠相比,用rPRA免疫并经腹腔注射强毒粗球孢子菌攻击的BALB/c小鼠的肺和脾中的真菌负荷大大降低。肺中的菌数减少了500倍,在免疫小鼠的脾脏中也观察到了类似的减少。这些研究支持将rPRA继续开发为预防球孢子菌病的候选疫苗。