Ma Yan-bing, Xie Tian-hong, Zhang Guang-ming, Li Chun-hong, Dai Xie-Jie, Dai Chang-bai, Sun Mao-sheng, Lu Jian, Bi Sheng-li
Department of Molecular Biology, Institute of Medical Biology, CAMS, PUMC, Kunming 650118, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Dec;24(6):592-5.
To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta).
Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR.
Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus.
The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.
观察重组抗原片段疫苗接种后恒河猴抗戊型肝炎病毒（HEV）IgG反应，并评估其对恒河猴戊型肝炎病毒感染的保护作用。
将12只猴子分为3组，分别用3种不同的重组抗原进行免疫：即Ag1（ORF2羧基末端431个氨基酸）、Ag2（ORF2羧基末端128个氨基酸片段）和Ag3（全长ORF3与由6743 - 7126nt和6287 - 6404nt编码的两个ORF2片段连接）。给猴子静脉注射来自实验感染恒河猴的粪便悬液进行攻毒，另外3只猴子作为戊型肝炎病毒攻毒的安慰剂组。检测丙氨酸氨基转移酶（ALT）水平和抗HEV IgG的动态变化。通过光学显微镜观察肝组织的病理变化。用逆转录巢式聚合酶链反应（RT - nPCR）检测病毒排泄情况。
安慰剂组2只猴子的肝脏组织病理学与急性病毒性肝炎一致，接种病毒后3 - 4周ALT升高，比正常水平高10 - 20倍。用抗原免疫的猴子肝脏组织保持正常，几只猴子的ALT轻度升高，接种疫苗后1 - 2周出现抗HEV IgG转换，滴度达到1:12,800。对照组猴子在第7天至第50天可通过RT - nPCR检测到病毒RNA，接种疫苗的猴子在攻毒后第7天至第21天可检测到病毒RNA。
重组抗原可诱导抗HEV IgG的产生，保护恒河猴免受与戊型肝炎病毒感染相关的急性肝炎症状。
