Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines.
Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines.
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DOI：
10.1038/s41467-022-28450-1
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发表时间：
2022-02-16
影响因子：
16.6
通讯作者：
Zolla-Pazner S
中科院分区：
文献类型：
--
作者：
Weiss S;Itri V;Pan R;Jiang X;Luo CC;Morris L;Malherbe DC;Barnette P;Alexander J;Kong XP;Haigwood NL;Hessell AJ;Duerr R;Zolla-Pazner S
对HIV gp 120包膜（Env）的V1 V2区中的表位具有特异性的V2 p和V2 i抗体（Ab）不能有效地中和HIV，但介导Fc依赖性抗病毒活性，这些活性与保护免受或控制HIV、SIV和SHIV感染相关。在这里，我们描述了一种新的分子工具箱，允许歧视的抗原性和功能不同的多克隆V2抗体的反应。我们确定了不同的模式V2抗体诱导SHIV感染和三个独立的疫苗方案，帮助微调优化的免疫方案诱导V2 p和V2 i抗体。我们在未接种疫苗的SHIV感染的NHP中观察到无或弱的和散发的V2 p和V2 i Ab，但在用V2靶向疫苗方案免疫后观察到强的V2 p和/或V2 i Ab应答。针对V2的疫苗接种在诱导功能性V2 p和V2 i特异性反应方面优于自然感染和用完整Env构建体免疫。上级。引人注目的是，V2定向的Ab水平与V3和C5肽特异性的Ab呈负相关。这些数据表明，V1 V2靶向疫苗具有优于SIV/SHIV感染和基于Env的完整免疫方案的不精确靶向的优点，用于诱导更集中的功能性V2 p和V2 i特异性Ab应答。在这里，作者表明，在非人灵长类动物中，将抗体集中在gp 120的V1 V2区域的HIV疫苗上级感染或用全包膜疫苗免疫，以诱导具有与保护相关的抗病毒功能的V1 V2抗体。
V2p and V2i antibodies (Abs) that are specific for epitopes in the V1V2 region of the HIV gp120 envelope (Env) do not effectively neutralize HIV but mediate Fc-dependent anti-viral activities that have been correlated with protection from, or control of HIV, SIV and SHIV infections. Here, we describe a novel molecular toolbox that allows the discrimination of antigenically and functionally distinct polyclonal V2 Ab responses. We identify different patterns of V2 Ab induction by SHIV infection and three separate vaccine regimens that aid in fine-tuning an optimized immunization protocol for inducing V2p and V2i Abs. We observe no, or weak and sporadic V2p and V2i Abs in non-vaccinated SHIV-infected NHPs, but strong V2p and/or V2i Ab responses after immunization with a V2-targeting vaccine protocol. The V2-focused vaccination is superior to both natural infection and to immunization with whole Env constructs for inducing functional V2p- and V2i-specific responses. Strikingly, levels of V2-directed Abs correlate inversely with Abs specific for peptides of V3 and C5. These data demonstrate that a V1V2-targeting vaccine has advantages over the imprecise targeting of SIV/SHIV infections and of whole Env-based immunization regimens for inducing a more focused functional V2p- and V2i-specific Ab response. Here the authors show that an HIV vaccine in non-human primates that focuses antibodies on the V1V2 region of gp120 is superior to infection or immunization with whole envelope vaccines for inducing V1V2 antibodies with anti-viral functions that correlate with protection.
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DOI：
10.1016/j.xcrm.2021.100290
发表时间：
2021-06-15
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Anand SP;Prévost J;Nayrac M;Beaudoin-Bussières G;Benlarbi M;Gasser R;Brassard N;Laumaea A;Gong SY;Bourassa C;Brunet-Ratnasingham E;Medjahed H;Gendron-Lepage G;Goyette G;Gokool L;Morrisseau C;Bégin P;Martel-Laferrière V;Tremblay C;Richard J;Bazin R;Duerr R;Kaufmann DE;Finzi A
通讯作者：
Finzi A
影响因子：
3.7
作者：
Gottardo R;Bailer RT;Korber BT;Gnanakaran S;Phillips J;Shen X;Tomaras GD;Turk E;Imholte G;Eckler L;Wenschuh H;Zerweck J;Greene K;Gao H;Berman PW;Francis D;Sinangil F;Lee C;Nitayaphan S;Rerks-Ngarm S;Kaewkungwal J;Pitisuttithum P;Tartaglia J;Robb ML;Michael NL;Kim JH;Zolla-Pazner S;Haynes BF;Mascola JR;Self S;Gilbert P;Montefiori DC
通讯作者：
Montefiori DC
DOI：
10.1016/s2352-3018(18)30071-7
发表时间：
2018-07
期刊：
The lancet. HIV
影响因子：
--
作者：
Bekker LG;Moodie Z;Grunenberg N;Laher F;Tomaras GD;Cohen KW;Allen M;Malahleha M;Mngadi K;Daniels B;Innes C;Bentley C;Frahm N;Morris DE;Morris L;Mkhize NN;Montefiori DC;Sarzotti-Kelsoe M;Grant S;Yu C;Mehra VL;Pensiero MN;Phogat S;DiazGranados CA;Barnett SW;Kanesa-Thasan N;Koutsoukos M;Michael NL;Robb ML;Kublin JG;Gilbert PB;Corey L;Gray GE;McElrath MJ;HVTN 100 Protocol Team
通讯作者：
HVTN 100 Protocol Team
影响因子：
5.4
作者：
GORNY, MK;MOORE, JP;ZOLLAPAZNER, S
通讯作者：
ZOLLAPAZNER, S
影响因子：
3.7
作者：
Gorny, Miroslaw K.;Pan, Ruimin;Zolla-Pazner, Susan
通讯作者：
Zolla-Pazner, Susan