CD8(+) T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication.
CD8(+) T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication.
复制标题
DOI：
10.1186/s12977-018-0429-y
复制
发表时间：
2018-07-03
期刊：
影响因子：
3.3
通讯作者：
Takiguchi M
中科院分区：
文献类型：
--
作者：
Murakoshi H;Zou C;Kuse N;Akahoshi T;Chikata T;Gatanaga H;Oka S;Hanke T;Takiguchi M
需要开发艾滋病疫苗，以有效预防艾滋病毒-1的传播，但没有试验表明对预防有明确的效果。最近的几项T细胞疫苗试验显示，尽管疫苗诱导了HIV-1特异性T细胞反应，但对HIV-1获取没有保护作用，这表明疫苗诱导的T细胞抑制HIV-1复制和/或交叉识别循环HIV-1的能力不足。因此，有必要开发T细胞疫苗，诱导T细胞识别具有较强抑制HIV-1能力的共享保护性表位。我们最近设计了t细胞镶嵌疫苗免疫原tHIVconsvX，由6个保守的Gag和Pol区组成，并证明了t细胞对疫苗免疫原衍生肽的反应与hiv -1感染，未接受治疗的日本个体的低血浆病毒载量（pVL）和高CD4+ t细胞计数（CD4计数）显着相关。然而，目前尚不清楚哪种特异性T细胞具有抑制HIV-1复制的能力。在本研究中，我们试图在疫苗免疫原中识别更多特异性保护性Gag表位的T细胞，并分析它们抑制HIV-1复制和识别循环HIV-1表位变异的能力。我们确定了17个最佳Gag表位及其HLA限制，发现t细胞对其中9个表位的反应与较低的pVL和/或较高的CD4计数显著相关。在221名hiv -1感染者中，即使比较具有相同限制性HLA等位基因的应答者和无应答者，识别5种Gag肽的t细胞仍然与良好的临床结果相关。虽然我们之前已经知道，这些保护性表位中的3个特异性T细胞在体内具有很强的抑制HIV-1复制的能力，但在这里，我们证明了这2个新的表位具有相同的能力。此外，针对所有5个Gag表位的T细胞在大多数循环HIV-1中交叉识别变异。我们证明了tHIVconsvX中5个Gag保守表位特异性的T细胞能够抑制HIV-1感染个体中循环HIV-1的复制。因此，tHIVconsvX疫苗具有正确的特异性，有助于预防HIV-1感染并在HIV-1再激活后根除潜伏感染的细胞。本文的在线版本（10.1186/s12977-018-0429-y）包含补充材料，授权用户可使用。
Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1. We recently designed T-cell mosaic vaccine immunogens tHIVconsvX composed of 6 conserved Gag and Pol regions and demonstrated that the T-cell responses to peptides derived from the vaccine immunogens were significantly associated with lower plasma viral load (pVL) and higher CD4+ T-cell count (CD4 count) in HIV-1-infected, treatment-naive Japanese individuals. However, it remains unknown T cells of which specificities have the ability to suppress HIV-1 replication. In the present study, we sought to identify more T cells specific for protective Gag epitopes in the vaccine immunogens, and analyze their abilities to suppress HIV-1 replication and recognize epitope variants in circulating HIV-1. We determined 17 optimal Gag epitopes and their HLA restriction, and found that T-cell responses to 9 were associated significantly with lower pVL and/or higher CD4 count. T-cells recognizing 5 of these Gag peptides remained associated with good clinical outcome in 221 HIV-1-infected individuals even when comparing responders and non-responders with the same restricting HLA alleles. Although it was known previously that T cells specific for 3 of these protective epitopes had strong abilities to suppress HIV-1 replication in vivo, here we demonstrated equivalent abilities for the 2 novel epitopes. Furthermore, T cells against all 5 Gag epitopes cross-recognized variants in majority of circulating HIV-1. We demonstrated that T cells specific for 5 Gag conserved epitopes in the tHIVconsvX have ability to suppress replication of circulating HIV-1 in HIV-1-infected individuals. Therefore, the tHIVconsvX vaccines have the right specificity to contribute to prevention of HIV-1 infection and eradication of latently infected cells following HIV-1 reactivation. The online version of this article (10.1186/s12977-018-0429-y) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
56.3
作者：
Gray, Glenda E.;Allen, Mai;Moodie, Zoe;Churchyard, Gavin;Bekker, Linda-Gail;Nchabeleng, Maphoshane;Mlisana, Koleka;Metch, Barbara;de Bruyn, Guy;Latka, Mary H.;Roux, Surita;Mathebula, Matsontso;Naicker, Nivashnee;Ducar, Constance;Carter, Donald K.;Puren, Adrien;Eaton, Niles;McElrath, M. Julie;Robertson, Michael;Corey, Lawrence;Kublin, James G.
通讯作者：
Kublin, James G.
影响因子：
7.4
作者：
Mothe B;Llano A;Ibarrondo J;Daniels M;Miranda C;Zamarreño J;Bach V;Zuniga R;Pérez-Álvarez S;Berger CT;Puertas MC;Martinez-Picado J;Rolland M;Farfan M;Szinger JJ;Hildebrand WH;Yang OO;Sanchez-Merino V;Brumme CJ;Brumme ZL;Heckerman D;Allen TM;Mullins JI;Gómez G;Goulder PJ;Walker BD;Gatell JM;Clotet B;Korber BT;Sanchez J;Brander C
通讯作者：
Brander C
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
影响因子：
64.5
作者：
Chung AW;Kumar MP;Arnold KB;Yu WH;Schoen MK;Dunphy LJ;Suscovich TJ;Frahm N;Linde C;Mahan AE;Hoffner M;Streeck H;Ackerman ME;McElrath MJ;Schuitemaker H;Pau MG;Baden LR;Kim JH;Michael NL;Barouch DH;Lauffenburger DA;Alter G
通讯作者：
Alter G