Postattachment neutralization of a primary strain of HIV type 1 in peripheral blood mononuclear cells is mediated by CD4-specific antibodies but not by a glycoprotein 120-specific antibody that gives potent standard neutralization.
Postattachment neutralization of a primary strain of HIV type 1 in peripheral blood mononuclear cells is mediated by CD4-specific antibodies but not by a glycoprotein 120-specific antibody that gives potent standard neutralization.
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DOI：
10.1089/088922201753342059
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发表时间：
2001-11
影响因子：
1.5
通讯作者：
T. McInerney;N. Dimmock
中科院分区：
文献类型：
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作者：
T. McInerney;N. Dimmock
从新感染HIV-1或从受感染细胞体内释放的病毒相对较快地附着在靶细胞上，但这种病毒的融合进入速度很慢，50%的进入>；或=2小时。因此，希望由任何疫苗刺激或在免疫治疗中给予的抗体不仅能够中和游离病毒，而且能够中和附着在靶细胞上的病毒。在这里，我们使用高效的gp120特异性人类单抗B12和针对CD4原代细胞受体的单抗，研究了外周血单核细胞中HIV-1主要毒株(JRCSF)和C8166 T淋巴母细胞中T细胞系适应株(IIIB)的后脱离中和(PAN)。此外，我们还改进了相关研究的实验方案，使用了一个抗体脉冲，从而避免了中和子代病毒的并发症。我们发现B12免疫球蛋白PAN是低效的，IIIB的PAN需要的抗体浓度是标准中和所需的1000倍，而JRCSF的PAN只有在4℃和非生理性的高浓度(300微克/毫升)下才能不稳定地检测到。然而，在相同的条件下，10微克/毫升的CD4特异性单抗Q4120脉冲就能释放99%的JRCSF PAN，即使在37℃下感染3小时后加入，也能释放95%以上的PAN。我们建议，这种抗CD4抗体应该被视为HIV-1免疫治疗的一个组成部分。
De novo infecting HIV-1 or virus released from an infected cell in vivo attaches relatively quickly to a target cell, but the rate of fusion-entry of such virus is slow, with 50% entry taking > or =2 hr. It is thus desirable that antibodies stimulated by any vaccine or given in immunotherapy are able to neutralize not only free virus, but also virus attached to the target cell. Here we investigated postattachment neutralization (PAN) of a primary HIV-1 strain (JRCSF) in peripheral blood mononuclear cells and of a T cell line-adapted strain (IIIB) in C8166 T lymphoblastoid cells, using the highly potent gp120-specific human monoclonal b12 monoclonal IgG, and monoclonal antibodies specific for the CD4 primary cell receptor. In addition, we improved the experimental protocols of related studies by using a pulse of antibody, thus avoiding the complication of neutralizing progeny virus. We found that b12 IgG PAN was inefficient, with PAN of IIIB needing a 1000-fold greater concentration of antibody than was required for standard neutralization, and PAN of JRCSF being detected erratically only at 4 degrees C and unphysiologically high concentrations (300 microg/ml). Nonetheless, under identical conditions a 10-microg/ml pulse of the CD4-specific MAb Q4120 gave up to 99% PAN of JRCSF, and more than 95% even when added 3 hr after infection at 37 degrees C. Possible mechanisms by which PAN by CD4- specific antibodies is mediated are discussed. We suggest that such anti-CD4 antibodies should be considered as a component of HIV-1 immunotherapy.