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通过用HSV-2复制缺陷型突变病毒免疫,在非致死性小鼠生殖器感染模型中预防生殖器疱疹疾病、血清转化和潜伏感染。

Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

作者信息

Diaz Fernando M, Knipe David M

机构信息

Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.

Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.

出版信息

Virology. 2016 Jan 15;488:61-7. doi: 10.1016/j.virol.2015.10.033. Epub 2015 Nov 21.

Abstract

Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved.

摘要

传统上,病毒疫苗可预防疾病,但对于会建立潜伏感染的病毒而言,理想的疫苗应能减少感染,从而降低潜伏感染及再激活的几率。虽然在单纯疱疹病毒(HSV)疫苗的临床试验中,血清转化已被用于衡量预防感染的效果,但在动物感染系统中尚未建立相关模型。为了评估一种生殖器疱疹候选疫苗针对感染各个方面的防护能力,我们建立了一种非致死性的小鼠生殖器HSV-2感染模型、一种用于检测针对感染细胞蛋白8(ICP8)特异性抗体的ELISA检测法,以及一种极为灵敏的qPCR检测法。通过这些检测法,我们观察到用HSV-2 dl5-29病毒进行免疫接种可减轻HSV-2攻击病毒所致的疾病、病毒脱落、血清转化及潜伏感染。因此,即使无法实现无菌免疫,通过免疫接种来预防生殖器疾病、血清转化及潜伏感染或许也是可行的。

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