Pinter A, Honnen W J, Kayman S C, Trochev O, Wu Z
Laboratory of Retroviral Biology, Public Health Research Institute, New York, NY 10016, USA.
Vaccine. 1998 Nov;16(19):1803-11. doi: 10.1016/s0264-410x(98)00182-0.
Although it is known that some human immune sera possess potent neutralizing activities for primary viruses, the identity of the target epitopes mediating this neutralization is unknown, and currently available immunogens have not been able to induce such activities. Using recombinant fusion glycoproteins expressing native V1/V2 domains of gp120 we have found that sera from a subset of HIV-1-infected humans contain antibodies that recognize broadly conserved V1/V2 epitopes. Such antibodies were isolated from one human serum by affinity chromatography on a column containing a V1/V2 fusion protein, and shown to efficiently neutralize several macrophage-tropic HIV-1 isolates. Rodents immunized with the purified V1/V2 fusion protein produced antibodies reactive with unrelated V1/V2 fusion proteins and with heterologous gp120s. V1/V2-specific immunoglobulins isolated from sera of these animals by affinity chromatography also possessed potent neutralization activity for several primary HIV-1 isolates. These results indicate that the V1/V2 domain of HIV-1 gp120 contains conserved epitopes that mediate potent neutralization of primary viruses, and suggest that subunit vaccines that efficiently induce such antibodies may provide protective humoral immunity against clinically relevant HIV-1 isolates.
虽然已知一些人免疫血清对原始病毒具有强大的中和活性，但介导这种中和作用的靶表位的身份尚不清楚，而且目前可用的免疫原无法诱导出这种活性。利用表达gp120天然V1/V2结构域的重组融合糖蛋白，我们发现来自一部分HIV-1感染人类的血清含有能识别广泛保守的V1/V2表位的抗体。通过在含有V1/V2融合蛋白的柱上进行亲和层析，从一份人血清中分离出了这类抗体，并证明它们能有效中和几种嗜巨噬细胞型HIV-1分离株。用纯化的V1/V2融合蛋白免疫的啮齿动物产生了与不相关的V1/V2融合蛋白以及异源gp120反应的抗体。通过亲和层析从这些动物血清中分离出的V1/V2特异性免疫球蛋白对几种原始HIV-1分离株也具有强大的中和活性。这些结果表明，HIV-1 gp120的V1/V2结构域含有介导对原始病毒进行有效中和的保守表位，并提示能有效诱导这类抗体的亚单位疫苗可能提供针对临床相关HIV-1分离株的保护性体液免疫。
