Background

HIV-1 infections occur following viral exposure at anogenital mucosal surfaces in the presence of semen. Semen contains immunosuppressive and pro-inflammatory factors. Semen from HIV-1-infected donors contains anti-HIV-1 antibodies. We assessed if passively infused anti-HIV-1 neutralizing antibody conferred protection from rectal SHIV_SF162P3 challenge at semen exposed mucosae.

Methods

We pooled seminal plasma from HIV-1-infected donors. The pool was screened by ELISA for antibodies against HIV-1_SF162 gp140. The ability of seminal plasma to inhibit macaque NK cells from responding to direct and antibody-dependent stimulation was assessed. The ability of seminal plasma to inhibit macaque granulocytes from mediating oxidative burst was also assessed. To demonstrate viral infectivity in the presence of seminal plasma, macaques (n = 4) were rectally challenged with SHIV_SF162P3 following exposure to 2.5 mL of seminal plasma. To evaluate if anti-HIV-1 neutralizing antibody confers protection against rectal SHIV challenge at semen exposed mucosae, eight macaques were intravenously infused with PGT121, either wild type (n = 4) or the Fc receptor binding deficient LALA variant (n = 4), and rectally challenged with SHIV_SF162P3 following exposure to 2.5 mL of seminal plasma.

Findings

Anti-HIV-1_SF162 gp140 antibodies were detected in seminal plasma. Seminal plasma inhibited direct and antibody-dependent NK cell activation and granulocyte oxidative burst in vitro. Rectal SHIV_SF162P3 challenge of control macaques following seminal plasma exposure resulted in infection of all animals. All macaques infused with wild type or LALA PGT121 and challenged with SHIV_SF162P3 following seminal plasma exposure were protected.

Interpretation

PGT121 conferred protection against rectal SHIV_SF162P3 challenge at semen exposed mucosae. Future research should investigate if semen alters protection conferred by antibodies more dependent on non-neutralizing functions.

中文翻译：

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抗 HIV 广泛中和抗体 PGT121 在精液暴露情况下的保护功效

背景

HIV-1 感染发生在存在精液的肛门生殖器黏膜表面病毒暴露后。精液含有免疫抑制和促炎因子。来自 HIV-1 感染供体的精液含有抗 HIV-1 抗体。我们评估了被动输注的抗 HIV-1 中和抗体是否能保护暴露于精液的黏膜免受直肠 SHIV _SF162P3攻击。

方法

我们汇集了来自 HIV-1 感染供体的精浆。通过 ELISA 筛选该池的针对 HIV-1 _SF162 gp140 的抗体。评估了精浆抑制猕猴 NK 细胞对直接和抗体依赖性刺激作出反应的能力。还评估了精浆抑制猕猴粒细胞介导氧化爆发的能力。为了证明存在精浆时的病毒感染性，猕猴 ( n  = 4) 在暴露于 2.5 mL 精浆后用 SHIV _{SF162P3进行直肠攻击。}为了评估抗 HIV-1 中和抗体是否能够保护暴露于精液的黏膜免受直肠 SHIV 攻击，八只猕猴被静脉输注了 PGT121，无论是野生型（n = 4) 或 Fc 受体结合缺陷型 LALA 变体 ( n  = 4)，并在暴露于 2.5 mL 精浆后用 SHIV _{SF162P3进行直肠攻击。}

发现

在精浆中检测到抗 HIV-1 _{SF162 gp140 抗体。}精浆在体外抑制直接和抗体依赖性NK细胞活化和粒细胞氧化爆发。暴露于精浆后的对照猕猴的直肠 SHIV _{SF162P3攻击导致所有动物感染。}所有注入野生型或 LALA PGT121 并在暴露于精浆后用 SHIV _{SF162P3攻击的猕猴都受到保护。}

解释

PGT121 对暴露于精液的黏膜具有抵抗直肠 SHIV _{SF162P3攻击的保护作用。}未来的研究应该调查精液是否会改变更依赖于非中和功能的抗体所赋予的保护作用。