Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3 loop and the CD4-binding site of gp120.
Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3 loop and the CD4-binding site of gp120.
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针对 V3 环和 gp120 的 CD4 结合位点的人单克隆抗体协同中和 HIV-1。
DOI：
10.1089/aid.1992.8.461
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发表时间：
1992
影响因子：
1.5
通讯作者：
Pinter,A
中科院分区：
文献类型：
--
作者：
Tilley,SA;Honnen,WJ;Racho,ME;Chou,TC;Pinter,A
人类免疫缺陷病毒1型（HIV-1）gp 120的两个不同区域或表位簇已被证明可引发中和抗体：V3环和CD 4结合位点。我们已经分离出了针对这两个区域中保守表位的中和性人单克隆抗体（HuMAb）。在这项研究中，我们证明了两种HuMAb的等摩尔混合物，一种针对V3环，另一种针对CD 4结合位点，中和HIV-1的浓度远低于任何一种单独的HuMAb。该效应的数学分析表明，两种HuMAb协同中和HIV-1，并显示出高水平的协同作用，MN和SF-2菌株90%中和的组合指数（CI）分别为0.07和0.16。两种HuMAb在99%中和时的剂量减少指数（DRI）范围约为10 - 150。通过与MN菌株的重组gp 160的结合研究提出了这种协同作用的可能机制;这些研究表明，在抗V3环HuMAb存在下，抗CD 4结合位点HuMAb的结合增强。这些结果证明了在针对HIV-1的疫苗中包括V3环和CD 4结合位点表位的优点，并表明针对这两个位点的HuMAb的组合在针对病毒的被动免疫治疗中可能特别有效。
Two distinct regions or epitope clusters of human immunodeficiency virus type 1 (HIV-1) gp120 have been shown to elicit neutralizing antibodies: the V3 loop and the CD4-binding site. We have isolated neutralizing human monoclonal antibodies (HuMAbs) against conserved epitopes in both of these regions. In this study, we demonstrate that an equimolar mixture of two of these HuMAbs, one directed against the V3 loop and the other against the CD4-binding site, neutralizes HIV-1 at much lower concentrations than does either of the individual HuMAbs. Mathematical analysis of this effect suggests cooperative neutralization of HIV-1 by the two HuMAbs and demonstrates a high level of synergy, with combination indices (CIs) of 0.07 and 0.16 for 90% neutralization of the MN and SF-2 strains, respectively. The dose reduction indices (DRIs) for each of the two HuMAbs at 99% neutralization range approximately from 10 to 150. A possible mechanism for this synergism is suggested by binding studies with recombinant gp160 of the MN strain; these show enhanced binding of the anti-CD4 binding site HuMAb in the presence of the anti-V3 loop HuMAb. These results demonstrate the advantage of including both V3 loop and CD4-binding site epitopes in a vaccine against HIV-1 and indicate that combinations of HuMAbs against these two sites may be particularly effective in passive immunotherapy against the virus.