Center for AIDS Research, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, MA 01605, USA.
Retrovirology. 2012 Jan 27;9:9. doi: 10.1186/1742-4690-9-9.
The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines. It is a priority to determine sites and structures within the CD4bs that are important for inclusion in vaccines. We studied a gp120 pocket penetrated by W100 of the potent CD4bs monoclonal antibody (mab), b12. We compared HIV-1 envelopes and corresponding mutants that carried blocked W100 pockets to evaluate whether other CD4bs mabs target this site.
All CD4bs mabs tested blocked soluble CD4 binding to gp120 consistent with their designation as CD4bs directed antibodies. All CD4bs mabs tested neutralized pseudovirions carrying NL4.3 wild type (wt) envelope. However, only b12 failed to neutralize pseudoviruses carrying mutant envelopes with a blocked W100 pocket. In addition, for CD4bs mabs that neutralized pseudovirions carrying primary envelopes, mutation of the W100 pocket had little or no effect on neutralization sensitivity.
Our data indicate that the b12 W100 pocket on gp120 is infrequently targeted by CD4bs mabs. This site is therefore not a priority for preservation in vaccines aiming to elicit antibodies targeting the CD4bs.
HIV-1 gp120 上的保守 CD4 结合位点（CD4bs）是疫苗的主要靶标。确定 CD4bs 中对包含在疫苗中很重要的位点和结构是当务之急。我们研究了 gp120 口袋，该口袋被强效 CD4bs 单克隆抗体（mab）b12 穿透。我们比较了 HIV-1 包膜和相应的突变体，这些突变体携带被阻断的 W100 口袋，以评估其他 CD4bs mab 是否靶向该位点。
所有测试的 CD4bs mab 均阻止可溶性 CD4 与 gp120 结合，这与其被指定为 CD4bs 定向抗体一致。所有测试的 CD4bs mab 均中和携带 NL4.3 野生型（wt）包膜的假病毒。然而，只有 b12 未能中和携带阻断 W100 口袋的突变包膜的假病毒。此外，对于中和携带原发性包膜的假病毒的 CD4bs mab，W100 口袋的突变对中和敏感性几乎没有影响。
我们的数据表明，gp120 上的 b12 W100 口袋很少被 CD4bs mab 靶向。因此，该位点不是旨在诱导针对 CD4bs 的抗体的疫苗中优先保留的靶标。
