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 V2 顶端抗原区的中和抗体是自然感染引起的最常见的交叉反应抗体之一。最近描述的两种 V2 特异性抗体 PGDM1400 和 CAP256-VRC26.25 已表现出针对 HIV-1 的卓越效力和中和广度。然而，关于 V2 特异性中和抗体的保护功效的数据很少。我们创建了一种新型 SHIV-325c 病毒原液，其中包含 C 型 HIV-1 包膜，并且易于被这两种抗体中和。在用 SHIV-325c 攻击之前，恒河猴接受了三种不同浓度（2、0.4 和 0.08 mg/kg）的单一抗体输注。 PGD​​M1400 在 0.4 mg/kg 剂量下具有完全保护性，而 CAP256-VRC26.25-LS 即使在 0.08 mg/kg 剂量下也具有完全保护性，这与其针对攻击病毒的更强的体外中和效力相关。对于CAP256-VRC26.25-LS，保护所需的血清抗体浓度为<0.75 μg/ml。这些数据证明了 V2 特异性中和抗体在非人灵长类动物中具有前所未有的效力和保护功效，并验证了 V2 作为人类被动免疫策略中预防 HIV-1 感染的潜在目标。