Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Sci Transl Med. 2017 Sep 6;9(406). doi: 10.1126/scitranslmed.aal1321.
Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth against HIV-1. However, little data exist on the protective efficacy of V2-specific neutralizing antibodies. We created a novel SHIV-325c viral stock that included a clade C HIV-1 envelope and was susceptible to neutralization by both of these antibodies. Rhesus macaques received a single infusion of either antibody at three different concentrations (2, 0.4, and 0.08 mg/kg) before challenge with SHIV-325c. PGDM1400 was fully protective at the 0.4 mg/kg dose, whereas CAP256-VRC26.25-LS was fully protective even at the 0.08 mg/kg dose, which correlated with its greater in vitro neutralization potency against the challenge virus. Serum antibody concentrations required for protection were <0.75 μg/ml for CAP256-VRC26.25-LS. These data demonstrate unprecedented potency and protective efficacy of V2-specific neutralizing antibodies in nonhuman primates and validate V2 as a potential target for the prevention of HIV-1 infection in passive immunization strategies in humans.
HIV-1 包膜 (Env) 三聚体的 V2 顶点抗原区的中和抗体是自然感染中最常见的交叉反应性抗体之一。最近描述的两种 V2 特异性抗体，PGDM1400 和 CAP256-VRC26.25，表现出针对 HIV-1 的极高效力和中和广度。然而，关于 V2 特异性中和抗体的保护效力的数据很少。我们创建了一种新型的 SHIV-325c 病毒株，该病毒株包含一个 clade C HIV-1 包膜，并且对这两种抗体都敏感。恒河猴在接受 SHIV-325c 挑战之前，分别以三种不同浓度（2、0.4 和 0.08 mg/kg）输注了这两种抗体中的一种。PGDM1400 在 0.4 mg/kg 剂量下完全具有保护作用，而 CAP256-VRC26.25-LS 甚至在 0.08 mg/kg 剂量下也完全具有保护作用，这与其对挑战病毒的更大体外中和效力相关。需要保护的血清抗体浓度<0.75 μg/ml 时，CAP256-VRC26.25-LS 起作用。这些数据表明 V2 特异性中和抗体在非人类灵长类动物中具有前所未有的效力和保护效力，并验证了 V2 作为被动免疫策略预防 HIV-1 感染的潜在靶标。
