Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai.
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
Curr Opin HIV AIDS. 2019 Jul;14(4):309-317. doi: 10.1097/COH.0000000000000551.
In humans, only one independent immunologic correlate of reduced risk of HIV infection has been identified: a robust antibody (Ab) response to the V1V2 domain of the gp120 envelope (Env) protein. In recent years, the presence and level of V1V2-specific Abs has also been correlated with protection from SIV and SHIV infections. Here, we review the multitude of studies showing the in-vivo protective effects of V1V2 Abs and review their immunologic characteristics and antiviral functions.
Structural and immunologic studies have defined four epitope families in the V1V2 domain: one epitope family, V2q, which preferentially presents as a quaternary structure of the Env trimer, and another epitope family (V2qt) which requires the quaternary trimeric Env structure; these two epitope types are recognized by two families of monoclonal Abs (mAbs)-V2q-specific and V2qt-specific mAbs-which display broad and potent neutralizing activity. A third epitope family, V2i, is present as a discontinuous conformational structure that overlays the α4β7 integrin binding motif, and a fourth epitope family (V2p) exists on V2 peptides. Antibodies specific for V2i and V2p epitopes display only poor neutralizing activity but effectively mediate other antiviral activities and have been correlated with control of and/or protection from HIV, SIV and SHIV. Notably, V2q and V2qt Abs have not been induced by any vaccines, but V2p and V2i Abs have been readily induced with various vaccines in nonhuman primates and humans.
The correlation of vaccine-induced V2p and V2i Abs with protection from HIV, SIV and SHIV suggests that these Ab types are extremely important to induce with prophylactic vaccines.
目的综述：在人类中，仅有一个独立的免疫相关因素被确定可以降低 HIV 感染风险：即对 gp120 包膜（Env）蛋白 V1V2 结构域具有强大的抗体（Ab）反应。近年来，V1V2 特异性 Ab 的存在和水平也与 SIV 和 SHIV 感染的保护作用相关。在此，我们综述了大量研究，这些研究表明 V1V2 Ab 具有体内保护作用，并对其免疫特征和抗病毒功能进行了综述。
最近发现：结构和免疫学研究已在 V1V2 结构域中定义了四个表位家族：一个表位家族 V2q，优先呈 Env 三聚体的四级结构，另一个表位家族（V2qt）需要四级三聚体 Env 结构；这两种表位类型被两种单克隆抗体（mAb）家族识别-V2q 特异性和 V2qt 特异性 mAb-它们具有广泛而强大的中和活性。第三个表位家族 V2i 呈不连续的构象结构，覆盖 α4β7 整合素结合基序，第四个表位家族（V2p）存在于 V2 肽上。针对 V2i 和 V2p 表位的抗体仅显示出较差的中和活性，但能有效地介导其他抗病毒活性，并与 HIV、SIV 和 SHIV 的控制和/或保护相关。值得注意的是，任何疫苗都未能诱导出 V2q 和 V2qt Ab，但 V2p 和 V2i Ab 很容易在非人类灵长类动物和人类中通过各种疫苗诱导产生。
总结：疫苗诱导的 V2p 和 V2i Ab 与 HIV、SIV 和 SHIV 的保护相关，这表明这些 Ab 类型对于预防性疫苗的诱导非常重要。
