Malenbaum S E, Yang D, Cheng-Mayer C
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
J Virol. 2001 Oct;75(19):9287-96. doi: 10.1128/JVI.75.19.9287-9296.2001.
We compared the immune responses to the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins in humans and macaques with the use of clade A and clade B isogenic V3 loop glycan-possessing and -deficient viruses. We found that the presence or absence of the V3 loop glycan affects to similar extents immune recognition by a panel of anti-HIV human and anti-simian/human immunodeficiency virus (anti-SHIV) macaque sera. All sera tested neutralized the glycan-deficient viruses, in which the conserved CD4BS and CD4i epitopes are more exposed, better than the glycan-containing viruses. The titer of broadly neutralizing antibodies appears to be higher in the sera of macaques infected with glycan-deficient viruses. Collectively, our data add legitimacy to the use of SHIV-macaque models for testing the efficacy of HIV-1 Env-based immunogens. Furthermore, they suggest that antibodies to the CD4BS and CD4i sites of gp120 are prevalent in human and macaque sera and that the use of immunogens in which these conserved neutralizing epitopes are more exposed is likely to increase their immunogenicity.
我们使用A亚型和B亚型同基因的含有V3环聚糖和缺乏V3环聚糖的病毒,比较了人类和猕猴对1型人类免疫缺陷病毒(HIV-1)包膜糖蛋白的免疫反应。我们发现,V3环聚糖的存在与否对一组抗HIV人类血清和抗猿猴/人类免疫缺陷病毒(抗SHIV)猕猴血清的免疫识别影响程度相似。所有测试血清对缺乏聚糖的病毒的中和能力均强于含聚糖的病毒,在缺乏聚糖的病毒中,保守的CD4结合位点(CD4BS)和CD4诱导表位(CD4i)更易暴露。感染缺乏聚糖病毒的猕猴血清中,广泛中和抗体的效价似乎更高。总体而言,我们的数据为使用SHIV-猕猴模型测试基于HIV-1包膜蛋白的免疫原的疗效提供了合理性依据。此外,这些数据表明,针对gp120的CD4BS和CD4i位点的抗体在人类和猕猴血清中普遍存在,使用这些保守中和表位更易暴露的免疫原可能会增强其免疫原性。