Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Vaccine. 2011 Sep 9;29(39):6802-9. doi: 10.1016/j.vaccine.2010.12.062. Epub 2011 Jan 1.
Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans.
鼠疫耶尔森菌(Y. pestis)是鼠疫的病原体,这种疾病的致死率极高,目前仍没有有效的疫苗,尤其是针对黏膜传播的疫苗。与许多细菌感染一样,抗原特异性抗体反应被传统上认为是疫苗诱导对 Y. pestis 保护的关键,如果不是唯一的原因。近年来的研究表明 T 细胞免疫反应对 Y. pestis 感染的重要性,但关于 Y. pestis 抗原特异性 T 细胞免疫反应的细节信息仍然有限。在目前的报告中,研究旨在确定 LcrV 蛋白(鼠疫疫苗开发的主要抗原)中 CD8+T 细胞表位的存在。此外,在 LcrV DNA 接种的 Balb/C 小鼠中耗尽 CD8+T 细胞会导致对 Y. pestis 致命鼻腔挑战的保护作用降低。这些发现确立了 LcrV DNA 疫苗能够针对这种关键鼠疫抗原的特定表位引发 CD8+T 细胞免疫反应,并且 CD8+T 细胞免疫反应参与了 LcrV DNA 疫苗引发的保护作用。未来的鼠疫疫苗开发研究需要检查是否存在可检测的 T 细胞免疫反应,特别是 CD8+T 细胞免疫反应,是否会增强高等动物或人类对 Y. pestis 的保护作用。