Ogata N, Ostberg L, Ehrlich P H, Wong D C, Miller R H, Purcell R H
Hepatitis Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3014-8. doi: 10.1073/pnas.90.7.3014.
The protective efficacy of a human monoclonal antibody directed against the a determinant of hepatitis B virus (HBV) surface antigen was studied in a chimpanzee. A single high dose of 5 mg/kg (body weight) of monoclonal antibody SDZ OST 577 was intravenously administered to a chimpanzee, followed by intravenous challenge with 10(3.5) chimpanzee infectious doses of a wild-type HBV, the MS-2 strain (ayw subtype). The passively acquired antibody to HBV surface antigen could be detected for 40 weeks. Serum HBV DNA tested by a "nested" polymerase chain reaction assay was negative through the 36th week after virus challenge but became positive by the 38th week. The chimpanzee subsequently developed acute hepatitis B approximately 1 year after challenge. The nucleotide sequence of the a determinant of the surface gene of the replicated virus was identical with that of the inoculated wild-type virus. Thus, a human monoclonal antibody directed against the a determinant of HBV surface antigen delayed but did not prevent experimental infection of HBV and hepatitis in the chimpanzee. Our results indicate an incomplete ability of this antibody to protect against HBV infection in vivo after a single infusion.
在一只黑猩猩身上研究了一种针对乙型肝炎病毒（HBV）表面抗原a决定簇的人源单克隆抗体的保护效力。给一只黑猩猩静脉注射单剂量5mg/kg（体重）的单克隆抗体SDZ OST 577，随后静脉注射10(3.5)个黑猩猩感染剂量的野生型HBV MS-2株（ayw亚型）进行攻击。被动获得的抗HBV表面抗原抗体可检测40周。通过“巢式”聚合酶链反应检测的血清HBV DNA在病毒攻击后第36周一直为阴性，但在第38周转为阳性。这只黑猩猩在攻击后约1年随后发生了急性乙型肝炎。复制病毒表面基因a决定簇的核苷酸序列与接种的野生型病毒相同。因此，针对HBV表面抗原a决定簇的人源单克隆抗体延迟但未预防黑猩猩的实验性HBV感染和肝炎。我们的结果表明，单次输注后该抗体在体内预防HBV感染的能力不完全。
