Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.
Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.
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DOI：
10.1038/nature20583
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发表时间：
2016-12-08
期刊：
影响因子：
64.8
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
--
作者：
Borducchi, Erica N.;Cabral, Crystal;Stephenson, Kathryn E.;Liu, Jinyan;Abbink, Peter;Ng'ang'a, David;Nkolola, Joseph P.;Brinkman, Amanda L.;Peter, Lauren;Lee, Benjamin C.;Jimenez, Jessica;Jetton, David;Mondesir, Jade;Mojta, Shanell;Chandrashekar, Abishek;Molloy, Katherine;Alter, Galit;Gerold, Jeffrey M.;Hill, Alison L.;Lewis, Mark G.;Pau, Maria G.;Schuitemaker, Hanneke;Hesselgesser, Joseph;Geleziunas, Romas;Kim, Jerome H.;Robb, Merlin L.;Michael, Nelson L.;Barouch, Dan H.
开发针对HIV-1感染者体内病毒库的免疫干预措施是HIV-1治疗领域的一个主要目标。然而，很少有证据表明，病毒库可以充分针对性地改善停止抗逆转录病毒治疗（ART）后的病毒学控制。本研究表明，刺激toll样受体7 （TLR7）的Ad26/MVA治疗性疫苗可以改善siv感染的恒河猴在急性感染期间开始抗逆转录病毒治疗后停止抗逆转录病毒治疗后的病毒学控制和病毒反弹。在病毒学抑制的siv感染猴子中，Ad26/MVA治疗性疫苗导致siv特异性细胞免疫反应的幅度和广度急剧增加。TLR7激动剂的使用导致先天免疫刺激和细胞免疫激活。Ad26/MVA疫苗接种和TLR7刺激联合使用可降低淋巴结和外周血中的病毒DNA水平，改善病毒控制并延迟ART停药后的病毒反弹。细胞免疫宽度与设定点病毒载量呈负相关，与病毒反弹时间直接相关。这些数据证明了先天性免疫刺激治疗性疫苗作为一种针对HIV-1功能性治愈的策略的潜力。
The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of the HIV-1 cure field. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy (ART). Here we show that Ad26/MVA therapeutic vaccination with toll-like receptor 7 (TLR7) stimulation improves virologic control and delays viral rebound following ART discontinuation in SIV-infected rhesus monkeys that initiated ART during acute infection. Ad26/MVA therapeutic vaccination resulted in a dramatic increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, as well as improved virologic control and delayed viral rebound following ART discontinuation. Cellular immune breadth correlated inversely with setpoint viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination with innate immune stimulation as a strategy aimed at an HIV-1 functional cure.
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影响因子：
4.3
作者：
De Boer RJ;Ribeiro RM;Perelson AS
通讯作者：
Perelson AS
DOI：
10.1073/pnas.0707449104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Chen, Hannah Yuan;Di Mascio, Michele;Zhang, Linqi
通讯作者：
Zhang, Linqi
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
4.3
作者：
Luzyanina, T;Engelborghs, K;Bocharov, G
通讯作者：
Bocharov, G
影响因子：
64.5
作者：
Ho YC;Shan L;Hosmane NN;Wang J;Laskey SB;Rosenbloom DI;Lai J;Blankson JN;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF