Verrier F, Nádas A, Gorny M K, Zolla-Pazner S
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
J Virol. 2001 Oct;75(19):9177-86. doi: 10.1128/JVI.75.19.9177-9186.2001.
Human immunodeficiency virus-type I (HIV-1) infection elicits antibodies (Abs) directed against several regions of the gp120 and gp41 envelope glycoproteins. Many of these Abs are able to neutralize T-cell-line-adapted strains (TCLA) of HIV-1, but only a few effectively neutralize primary HIV-1 isolates. The nature of HIV-1 neutralization has been carefully studied using human monoclonal Abs (MAbs), and the ability of such MAbs to act in synergy to neutralize HIV-1 has also been extensively studied. However, most synergy studies have been conducted using TCLA strains. To determine the nature of Ab interaction in HIV-1 primary isolate neutralization, a panel of 12 anti-HIV-1 human immunoglobulin G (IgG) MAbs, specific for epitopes in gp120 and gp41, were used. Initial tests showed that six of these MAbs, as well as sCD4, used individually, were able to neutralize the dualtropic primary isolate HIV-1(89.6); MAbs giving significant neutralization at 2 to 10 microg/ml included 2F5 (anti-gp41), 50-69 (anti-gp41), IgG1b12 (anti-gp120(CD4bd)), 447-52D (anti-gp120(V3)), 2G12 (anti-gp120), and 670-D (anti-gp120(C5)). For studies of reagent interaction, 16 binary combinations of reagents were tested for their ability to neutralize HIV-1(89.6). Reagent combinations tested included one neutralizing MAb with sCD4, six pairs consisting of two neutralizing MAbs, and nine pairs consisting of one neutralizing MAb with another non-neutralizing MAb. To assess the interaction of the latter type of combination, a new mathematical treatment of reagent interaction was developed since previously used methods could be used only when both reagents neutralize. Synergy was noted between sCD4 and a neutralizing anti-gp120(V3) MAb. Antagonism was noted between two pairs of anti-gp41 MAbs (one neutralizing and one non-neutralizing). All of the other 13 pairs of MAbs tested displayed only additive effects. These studies suggest that Abs rarely act in synergy to neutralize primary isolate HIV-1(89.6); many anti-HIV-1 Abs act additively to mediate this biological function.
I型人类免疫缺陷病毒（HIV-1）感染可引发针对gp120和gp41包膜糖蛋白多个区域的抗体（Abs）。其中许多抗体能够中和HIV-1的T细胞系适应株（TCLA），但只有少数能有效中和HIV-1原代分离株。利用人单克隆抗体（MAbs）对HIV-1中和的本质进行了仔细研究，并且也广泛研究了此类单克隆抗体协同中和HIV-1的能力。然而，大多数协同作用研究是使用TCLA毒株进行的。为了确定HIV-1原代分离株中和中抗体相互作用的本质，使用了一组12种抗HIV-1人免疫球蛋白G（IgG）单克隆抗体，它们对gp120和gp41中的表位具有特异性。初步试验表明，这些单克隆抗体中的六种以及单独使用的可溶性CD4（sCD4）能够中和双嗜性原代分离株HIV-1(89.6)；在2至10微克/毫升时产生显著中和作用的单克隆抗体包括2F5（抗gp41）、50-69（抗gp41）、IgG1b12（抗gp120(CD4结合域)）、447-52D（抗gp120(V3)）、2G12（抗gp120）和670-D（抗gp120(C5)）。为了研究试剂相互作用，测试了16种试剂二元组合中和HIV-1(89.6)的能力。测试的试剂组合包括一种中和单克隆抗体与sCD4、由两种中和单克隆抗体组成的六对组合以及由一种中和单克隆抗体与另一种非中和单克隆抗体组成的九对组合。为了评估后一种组合类型的相互作用，开发了一种新的试剂相互作用数学处理方法，因为以前使用的方法仅在两种试剂都具有中和作用时才能使用。观察到sCD4与一种中和抗gp120(V3)单克隆抗体之间存在协同作用。在两对抗gp41单克隆抗体（一对中和性和一对非中和性）之间观察到拮抗作用。测试的所有其他13对单克隆抗体仅表现出相加作用。这些研究表明，抗体很少协同作用来中和原代分离株HIV-1(89.6)；许多抗HIV-1抗体通过相加作用来介导这种生物学功能。
