[Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.
Ma
Yan-bing
YB
Department of Molecular Biology, Institute of Medical Biology, CAMS, PUMC, Kunming 650118, China. mayanbing1969@163.net
Xie
Tian-hong
TH
Zhang
Guang-ming
GM
Li
Chun-hong
CH
Dai
Xie-Jie
XJ
Dai
Chang-bai
CB
Sun
Mao-sheng
MS
Lu
Jian
J
Bi
Sheng-li
SL
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D016751:Hepatitis E / Q000517:prevention & control*; D016752:Hepatitis E virus / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D000956:Antigens, Viral; D007074:Immunoglobulin G; D012367:RNA, Viral; D011994:Recombinant Proteins; D014761:Viral Hepatitis Vaccines