Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys.
Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys.
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作者：
最近描述了具有非凡效力和广度的HIV-1特异性单抗。在人源化的小鼠身上，单抗的组合已经被证明可以抑制病毒血症，但这些单抗在免疫系统完整的灵长类动物中的治疗潜力尚未得到评估。在这里，我们展示了注射HIV-1特异性单抗的鸡尾酒，以及单一的依赖糖的单抗PGT121，导致慢性感染致病病毒Shiv-SF162P3的恒河猴血浆病毒血症迅速和急剧下降到无法检测到的水平。一次单抗注射后，血浆病毒RNA在7天内下降了3.1个对数，外周血、胃肠道粘膜和淋巴结中的前病毒DNA也减少了，而没有产生病毒耐药性。此外，在给予mAb后，宿主Gag特异性T淋巴细胞反应显示出更好的功能。在血清mAb滴度下降到无法检测到的水平的中位数56天后，大多数动物的病毒出现反弹，尽管有一部分动物在没有进一步注射mAb的情况下保持了长期的病毒学控制。这些数据表明，强有力的中和HIV-1特异性单抗对感染SHV病毒的恒河猴有深刻的治疗效果，并对宿主免疫反应产生影响。我们的发现有力地鼓励了对人类HIV-1单抗治疗的研究。
HIV-1-specific monoclonal antibodies (mAbs) with extraordinary potency and breadth have recently been described. In humanized mice, combinations of mAbs have been shown to suppress viremia, but the therapeutic potential of these mAbs has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific mAbs, as well as the single glycan-dependent mAb PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic virus SHIV-SF162P3. A single mAb infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance. Moreover, following mAb administration, host Gag-specific T lymphocyte responses exhibited improved functionality. Virus rebounded in the majority of animals after a median of 56 days when serum mAb titers had declined to undetectable levels, although a subset of animals maintained long-term virologic control in the absence of further mAb infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific mAbs in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of mAb therapy for HIV-1 in humans.
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影响因子：
16.8
作者：
Kong, Leopold;Lee, Jeong Hyun;Doores, Katie J.;Murin, Charles D.;Julien, Jean-Philippe;McBride, Ryan;Liu, Yan;Marozsan, Andre;Cupo, Albert;Klasse, Per-Johan;Hoffenberg, Simon;Caulfield, Michael;King, C. Richter;Hua, Yuanzi;Le, Khoa M.;Khayat, Reza;Deller, Marc C.;Clayton, Thomas;Tien, Henry;Feizi, Ten;Sanders, Rogier W.;Paulson, James C.;Moore, John P.;Stanfield, Robyn L.;Burton, Dennis R.;Ward, Andrew B.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
通讯作者：
Connors M
影响因子：
64.8
作者：
通讯作者：
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影响因子：
5.4
作者：
Mehandru, Saurabh;Vcelar, Brigitta;Markowitz, Martin
通讯作者：
Markowitz, Martin
影响因子：
5.4
作者：
Li, Hualin;Liu, Jinyan;Barouch, Dan H.
通讯作者：
Barouch, Dan H.