Wang C Y, Sawyer L S, Murthy K K, Fang X, Walfield A M, Ye J, Wang J J, Chen P D, Li M L, Salas M T, Shen M, Gauduin M C, Boyle R W, Koup R A, Montefiori D C, Mascola J R, Koff W C, Hanson C V
United Biomedical Inc., 25 Davids Drive, Hauppauge, NY 11788, USA.
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10367-72. doi: 10.1073/pnas.96.18.10367.
mAb B4 is a monoclonal antibody directed against HIV receptor complex. The antibody had broad neutralizing activity against HIV and provided postexposure prophylaxis to hu-peripheral blood leukocyte (PBL)-severe combined immunodeficient mice and chimpanzees. B4 recognized a complex receptor site for HIV on the T cell surface that includes CD4 and also may be influenced by interaction with HIV coreceptors. mAb B4 preferentially neutralized primary HIV-1 isolates compared with T cell line-adapted strains, including syncytium-inducing and non-syncytium-inducing phenotypes, representatives from HIV-1 subtypes A-G, as well as HIV-2, simian immunodeficiency virus, and chimeric simian/human immunodeficiency virus (SHIV). Neutralization was demonstrated in both pre- and postinfection models. The administration of mAb B4 after infectious challenge totally interrupted the infection of hu-PBL-severe combined immunodeficient mice by PBL-grown HIV-1 and the infection of chimpanzees by chimp-adapted HIV-1. This mode of protection suggested that the anti-HIV receptor antibody is efficacious for prophylaxis after exposure to HIV and for prevention of maternal transmission and may be an effective antiretroviral agent for treatment.
单克隆抗体B4是一种针对HIV受体复合物的单克隆抗体。该抗体对HIV具有广泛的中和活性,并为人类外周血白细胞(PBL)-严重联合免疫缺陷小鼠和黑猩猩提供暴露后预防。B4识别T细胞表面HIV的一个复合受体位点,该位点包括CD4,并且可能受与HIV共受体相互作用的影响。与适应T细胞系的毒株相比,单克隆抗体B4优先中和原发性HIV-1分离株,包括合胞体诱导型和非合胞体诱导型表型、HIV-1 A-G亚型的代表,以及HIV-2、猴免疫缺陷病毒和嵌合猴/人免疫缺陷病毒(SHIV)。在感染前和感染后模型中均证实了中和作用。在感染性攻击后给予单克隆抗体B4完全阻断了PBL培养的HIV-1对人类PBL-严重联合免疫缺陷小鼠的感染以及黑猩猩适应的HIV-1对黑猩猩的感染。这种保护模式表明,抗HIV受体抗体在暴露于HIV后用于预防以及预防母婴传播方面是有效的,并且可能是一种有效的抗逆转录病毒治疗药物。