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食蟹猴针对戊型肝炎的成功被动和主动免疫。

Successful passive and active immunization of cynomolgus monkeys against hepatitis E.

作者信息

Tsarev S A, Tsareva T S, Emerson S U, Govindarajan S, Shapiro M, Gerin J L, Purcell R H

机构信息

Hepatitis Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

出版信息

Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10198-202. doi: 10.1073/pnas.91.21.10198.

DOI:10.1073/pnas.91.21.10198
PMID:7937861
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC44985/
Abstract

Virtually full protection against hepatitis E and partial or complete protection against infection with hepatitis E virus (HEV) were achieved in passively or actively immunized cynomolgus monkeys. Hepatitis, viremia, and shedding of the virus in feces were detected in all nonimmunized animals that were challenged with HEV. HEV titers detected by reverse transcriptase PCR were higher in feces than in serum of nonimmunized animals. Anti-HEV antibody titers at the time of challenge ranged between 1:40 and 1:200 in animals passively immunized with convalescent plasma from a cynomolgus monkey previously infected with HEV and between 1:100 and 1:10,000 in animals actively immunized with a recombinant 55-kDa open reading frame 2 protein. The estimated 50% protective titer of passively acquired anti-HEV antibodies was 1:40. Although only one of four passively immunized animals showed histopathologic evidence of hepatitis, all four were infected after challenge; however, the titers of HEV in serum and feces were lower in the passively immunized animals than in the nonimmunized group. The actively immunized animals developed neither hepatitis nor viremia when challenged with HEV and virus was either not detected or was present in low titer in feces. The protective response was a function of the ELISA anti-HEV antibody titer at the time of challenge and the immunization schedule.

摘要

在被动或主动免疫的食蟹猴中,实现了对戊型肝炎的几乎完全保护以及对戊型肝炎病毒(HEV)感染的部分或完全保护。在用HEV攻击的所有未免疫动物中,均检测到肝炎、病毒血症以及粪便中病毒的排出。通过逆转录酶PCR检测到的未免疫动物粪便中的HEV滴度高于血清中的滴度。在用先前感染HEV的食蟹猴的恢复期血浆进行被动免疫的动物中,攻击时的抗HEV抗体滴度在1:40至1:200之间,在用重组55 kDa开放阅读框2蛋白进行主动免疫的动物中,抗HEV抗体滴度在1:100至1:10,000之间。被动获得的抗HEV抗体的估计50%保护滴度为1:40。虽然四只被动免疫动物中只有一只显示出肝炎的组织病理学证据,但所有四只在攻击后均被感染;然而,被动免疫动物血清和粪便中的HEV滴度低于未免疫组。在用HEV攻击时,主动免疫的动物既未发生肝炎也未出现病毒血症,粪便中要么未检测到病毒,要么病毒滴度很低。保护反应是攻击时ELISA抗HEV抗体滴度和免疫方案的函数。

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本文引用的文献

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Variation in course of hepatitis E in experimentally infected cynomolgus monkeys.实验感染食蟹猴中戊型肝炎病程的变化
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ELISA for antibody to hepatitis E virus (HEV) based on complete open-reading frame-2 protein expressed in insect cells: identification of HEV infection in primates.基于昆虫细胞中表达的戊型肝炎病毒(HEV)完整开放阅读框2蛋白的戊型肝炎病毒抗体酶联免疫吸附测定:灵长类动物中戊型肝炎病毒感染的鉴定
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J Med Virol. 1993 Sep;41(1):90-4. doi: 10.1002/jmv.1890410118.
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J Med Virol. 1994 Jun;43(2):135-42. doi: 10.1002/jmv.1890430207.
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Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease.巴基斯坦戊型肝炎流行:血清学反应模式及戊型肝炎病毒抗体可预防疾病的证据
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Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology.印度的流行性和地方性肝炎:非甲非乙型肝炎病毒病因学的证据。
Lancet. 1980 Oct 25;2(8200):876-9. doi: 10.1016/s0140-6736(80)92045-0.