In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees

In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees
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DOI:
10.1016/j.virol.2003.09.014
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发表时间:
2004-01-05
期刊:
影响因子:
3.7
通讯作者:
Park, SY
Park, SY
中科院分区:
医学3区
文献类型:
--
作者:
Hong, HJ;Ryu, CJ;Park, SY

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此前,我们制备了一种小鼠单克隆抗体(mAb) KR127,该抗体可识别乙型肝炎病毒(HBV) preSI的37-45氨基酸。在这项研究中,我们构建了KR127的人源化版本,并评估了其在黑猩猩中的hbv中和活性。研究黑猩猩被给予单次静脉剂量的人源化抗体,随后静脉注射野生型HBV的adr亚型,而对照组黑猩猩只注射病毒。结果表明,研究黑猩猩在1年内没有发生HBV感染,而对照组黑猩猩感染了HBV,这表明人源化抗体具有体内病毒中和活性,从而保护黑猩猩免受HBV感染。此外,人源化抗体与所有HBV亚型的preS1结合。我们首先证明了抗pres1单抗可以在体内中和HBV感染。该人源化抗体可用于HBV感染的免疫预防。(C) 2003 Elsevier Inc.版权所有。
Previously, we generated a murine monoclonal antibody (mAb), KR127, that recognizes amino acids (aa) 37-45 of the preSI of hepatitis B virus (HBV). In this study, we have constructed a humanized version of KR127 and evaluated its HBV-neutralizing activity in chimpanzees. A study chimpanzee was given a single intravenous dose of the humanized antibody, followed by intravenous challenge with adr subtype of wild type HBV, while a control chimpanzee was only challenged with the virus. The result showed that the study chimpanzee did not develop HBV infection during 1 year, while the control chimpanzee was infected, indicating that the humanized antibody exhibited in vivo virus-neutralizing activity and thus protected the chimpanzee from HBV infection. In addition, the humanized antibody bound to the preS1 of all subtypes of HBV. We first demonstrate that an anti-preS1 mAb can neutralize HBV infection in vivo. This humanized antibody will be useful for the immunoprophylaxis of HBV infection. (C) 2003 Elsevier Inc. All rights reserved.