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CD8+T 细胞介导的免疫应答参与 LcrV DNA 疫苗诱导的抗致死性鼠疫耶尔森菌感染的保护作用。

Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge.

机构信息

Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

出版信息

Vaccine. 2011 Sep 9;29(39):6802-9. doi: 10.1016/j.vaccine.2010.12.062. Epub 2011 Jan 1.

Abstract

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.

摘要

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。

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