Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.
Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.
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DOI：
10.1038/nm.4063
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发表时间：
2016-04
期刊：
影响因子：
82.9
通讯作者：
Haigwood NL
中科院分区：
文献类型：
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作者：
Hessell AJ;Jaworski JP;Epson E;Matsuda K;Pandey S;Kahl C;Reed J;Sutton WF;Hammond KB;Cheever TA;Barnette PT;Legasse AW;Planer S;Stanton JJ;Pegu A;Chen X;Wang K;Siess D;Burke D;Park BS;Axthelm MK;Lewis A;Hirsch VM;Graham BS;Mascola JR;Sacha JB;Haigwood NL
在产前护理不易获得的地区，预防艾滋病毒母婴传播 (MTCT) 仍然是一个主要目标。我们在婴儿猕猴模型中测试了抗 HIV-1 人中和单克隆抗体 (NmAb) 作为暴露后治疗的产时 MTCT。一个月大的恒河猴口服接种 SHIVSF162P3。在病毒暴露后第 1、4、7 和 10 天，我们给动物皮下注射 NmAb，并在给药后 24 小时内量化 NmAb 在多个组织中的全身分布。第一天，未经治疗的动物体内多个组织中就发现了复制病毒。所有接受 NmAb 治疗的猕猴在暴露后 6 个月时血液和组织中均不含病毒。我们在尸检时在血液或组织中没有检测到抗 SHIV T 细胞反应，并且 CD8+ T 细胞耗尽后没有病毒出现。这些结果表明早期被动免疫疗法可以消除早期病毒病灶，从而防止病毒储存库的建立。
Prevention of mother to child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested anti-HIV-1 human neutralizing monoclonal antibodies (NmAb) as post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with SHIVSF162P3. On days 1, 4, 7, and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h following administration. Replicating virus was found in multiple tissues by day 1 in animals without treatment. All NmAb-treated macaques were free of virus in blood and tissues at 6 months post-exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged following CD8+ T cell depletion. These results suggest early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.