Khouri Y F, McIntosh K, Cavacini L, Posner M, Pagano M, Tuomala R, Marasco W A
Dana-Farber Cancer Institute, Division of Human Retrovirology, Boston, Massachusetts 02115.
J Clin Invest. 1995 Feb;95(2):732-7. doi: 10.1172/JCI117720.
Almost all childhood HIV-1 is now acquired through vertical transmission. Identifying factors that affect the rate of transmission may lead to the initiation of specific preventive strategies. In this study, antibody levels against different neutralizing epitopes on the envelope glycoprotein of HIV-1 (gp120) were measured in HIV-1-infected pregnant women that either transmitted HIV-1 to their infants (18 women) or did not (29 women). Differences in levels of antibodies directed against the monomeric gp120 molecule and against the V3 loop region of gp120 were not significantly different between the two groups studied. However, significant differences were observed in the levels of CD4 binding site antibodies, as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 (mAb F105) to monomeric gp120. In addition, more nontransmitting mothers had low viral load as defined by having two or more negative HIV-1 viral cultures during pregnancy compared with transmitters. This pilot study suggests that in addition to higher viral load, low levels of CD4 binding site antibodies correlate with increased risk of HIV-1 vertical transmission. Passive immunotherapy with broadly neutralizing CD4 binding site antibodies should be considered as a strategy to reduce this risk.
目前,几乎所有儿童HIV-1感染都是通过垂直传播获得的。识别影响传播率的因素可能会促使启动特定的预防策略。在本研究中,对感染HIV-1的孕妇进行了检测,这些孕妇要么将HIV-1传播给了她们的婴儿(18名女性),要么没有(29名女性),检测她们针对HIV-1包膜糖蛋白(gp120)上不同中和表位的抗体水平。在研究的两组之间,针对单体gp120分子和gp120的V3环区域的抗体水平差异不显著。然而,通过稀释的母体血浆抑制CD4结合位点单克隆抗体F105(mAb F105)与单体gp120结合的能力来测定,发现两组在CD4结合位点抗体水平上存在显著差异。此外,与传播者相比,更多未传播的母亲在孕期有两次或更多次HIV-1病毒培养阴性,即病毒载量较低。这项初步研究表明,除了较高的病毒载量外,CD4结合位点抗体水平低与HIV-1垂直传播风险增加相关。应考虑采用具有广泛中和作用的CD4结合位点抗体进行被动免疫治疗,作为降低这种风险的一种策略。