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Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-11-01 , DOI: 10.1038/s41385-018-0067-7
Jonathon E Himes 1 , Ria Goswami 1 , Riley J Mangan 1 , Amit Kumar 1 , Thomas L Jeffries 1 , Joshua A Eudailey 1 , Holly Heimsath 1 , Quang N Nguyen 1 , Justin Pollara 1, 2 , Celia LaBranche 1 , Meng Chen 1 , Nathan A Vandergrift 1 , James W Peacock 1 , Faith Schiro 3 , Cecily Midkiff 3 , Guido Ferrari 1, 2 , David C Montefiori 1 , Xavier Alvarez Hernandez 3 , Pyone Pyone Aye 3 , Sallie R Permar 1, 4, 5, 6
Affiliation  

Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to untreated HIV-infected mothers become infected. This study assessed the protective capacity of natural HIV envelope-specific antibodies isolated from the milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and milk maternal antibody transfer, infant RMs were i.v. infused and orally treated at the time of challenge with a single weakly neutralizing milk monoclonal antibody (mAb), a tri-mAb cocktail with weakly neutralizing and ADCC functionalities, or an anti-influenza control mAb. Of these groups, the fewest tri-mAb-treated infants had SHIV detectable in plasma or tissues (2/6, 5/6, and 7/8 animals infected in tri-mAb, single-mAb, and control-mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer plasma transmitted/founder variants and reduced peripheral CD4+ T cell proviral loads at 8 weeks post-challenge compared to control mAb-treated infants. Abortive infection was observed as detectable CD4+ T cell provirus in non-viremic control mAb- and single mAb-, but not in tri-mAb-treated animals. These results suggest that polyfunctional milk antibodies contribute to the natural inefficiency of HIV-1 transmission through breastfeeding and infant vaccinations eliciting non-neutralizing antibody responses could reduce postnatal HIV transmission.

中文翻译:

多克隆 HIV 包膜特异性母乳抗体限制了幼年恒河猴的创始人 SHIV 获取和细胞相关病毒载量。

母乳 HIV-1 传播目前是儿童 HIV 感染的主要原因。然而,未经治疗的 HIV 感染母亲所生的母乳喂养婴儿中只有约 10% 会被感染。本研究评估了在婴儿恒河猴 (RM) 2 级 SHIV 口服攻击模型中从感染 HIV 的妇女的乳汁中分离出的天然 HIV 包膜特异性抗体的保护能力。为了模拟胎盘和乳汁母体抗体转移,婴儿 RM 在攻击时用单一的弱中和乳汁单克隆抗体 (mAb)、具有弱中和和 ADCC 功能的 tri-mAb 混合物或抗-流感对照单克隆抗体。在这些组中,最少的经 tri-mAb 治疗的婴儿在血浆或组织中检测到 SHIV(2/6、5/6 和 7/8 的动物感染了 tri-mAb、单-mAb、和对照-mAb 组)。与对照 mAb 治疗的婴儿相比,Tri-mAb 治疗的婴儿在攻击后 8 周表现出显着更少的血浆传播/创始人变异和减少的外周 CD4+ T 细胞前病毒载量。在非病毒血症对照 mAb- 和单一 mAb- 中观察到流产感染作为可检测的 CD4+ T 细胞原病毒,但在 tri-mAb 处理的动物中没有观察到。这些结果表明,多功能乳汁抗体通过母乳喂养导致 HIV-1 自然传播效率低下,而婴儿疫苗接种引发非中和抗体反应可以减少产后 HIV 传播。与对照 mAb 治疗的婴儿相比,Tri-mAb 治疗的婴儿在攻击后 8 周表现出显着更少的血浆传播/创始人变异和减少的外周 CD4+ T 细胞前病毒载量。在非病毒血症对照 mAb- 和单一 mAb- 中观察到流产感染作为可检测的 CD4+ T 细胞原病毒,但在 tri-mAb 处理的动物中没有观察到。这些结果表明,多功能乳汁抗体通过母乳喂养导致 HIV-1 自然传播效率低下,而婴儿疫苗接种引发非中和抗体反应可以减少产后 HIV 传播。与对照 mAb 治疗的婴儿相比,Tri-mAb 治疗的婴儿在攻击后 8 周表现出显着更少的血浆传播/创始人变异和减少的外周 CD4+ T 细胞前病毒载量。在非病毒血症对照 mAb- 和单一 mAb- 中观察到流产感染作为可检测的 CD4+ T 细胞原病毒,但在 tri-mAb 处理的动物中没有观察到。这些结果表明,多功能乳汁抗体通过母乳喂养导致 HIV-1 自然传播效率低下,而婴儿疫苗接种引发非中和抗体反应可以减少产后 HIV 传播。
更新日期:2018-08-17
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