Identification of gp120 Regions Targeted by a Highly Potent Neutralizing Antiserum Elicited in a Chimpanzee Inoculated with a Primary Human Immunodeficiency Virus Type 1 Isolate

We have previously reported that a chimpanzee infected with a primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1(DH12)) developed an extremely potent virus-neutralizing antibody. Immunoglobulin G purified from this animal conferred sterilizing immunity following passive transfer to macaques which were subsequently challenged with simian immunodeficiency virus/HIV-1 chimeric virus strain DH12. In addition to being highly strain specific, the chimpanzee antiserum did not bind to the V3 loop peptide of HIV-1(DH12), nor did it block the interaction of gp120 with the CD4 receptor. When neutralization was examined in the context of virus particles carrying chimeric envelope glycoproteins, the presence of all five hypervariable regions (V1 to V5) was required for optimal neutralization. Virions bearing chimeric gp120 containing the V1–V2 and V4 regions of HIV-1(DH12) could also be neutralized, but larger quantities of the chimpanzee antiserum were needed to block infection. These results indicate that the HIV-1 gp120 epitope(s) targeted by the chimpanzee antiserum is highly conformational, involving surface elements contributed by all of the hypervariable domains of the envelope glycoprotein.

此前我们已有报道：一株原发性人类免疫缺陷病毒1型（human immunodeficiency virus type 1, HIV-1）分离株（HIV-1(DH12)）感染黑猩猩后，该黑猩猩体内产生了效力极强的病毒中和抗体。从该动物体内纯化得到的免疫球蛋白G（Immunoglobulin G, IgG）经被动免疫转移至猕猴后，可赋予后者清除性免疫，使其在后续接受猴免疫缺陷病毒/HIV-1嵌合病毒株DH12攻毒时免受感染。
该黑猩猩抗血清除具有高度的毒株特异性外，既不结合HIV-1(DH12)的V3环肽，也不会阻断gp120与CD4受体（CD4 receptor）的相互作用。当在携带嵌合包膜糖蛋白的病毒颗粒环境中检测中和活性时，实现最优中和效果需要病毒包膜包含全部5个高变区（V1至V5）。仅携带HIV-1(DH12) V1–V2和V4区的嵌合gp120的病毒体也可被中和，但需要使用更高剂量的黑猩猩抗血清才能阻断感染。
上述结果表明，该黑猩猩抗血清所靶向的HIV-1 gp120表位具有高度的构象依赖性，其抗原表位由包膜糖蛋白所有高变结构域贡献的表面结构元件共同构成。