Definition of the viral targets of protective HIV-1-specific T cell responses.
Definition of the viral targets of protective HIV-1-specific T cell responses.
复制标题
DOI：
10.1186/1479-5876-9-208
复制
发表时间：
2011-12-07
影响因子：
7.4
通讯作者：
Brander C
中科院分区：
文献类型：
--
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
未来HIV-1疫苗的CTL组分的功效将取决于具有最有效的抗病毒活性和广泛的HLA I类限制的应答的诱导。然而，目前的HIV疫苗设计在很大程度上仅基于病毒序列比对，而没有结合关于T细胞功能和特异性的实验数据。在此，测试了950个未经治疗的HIV-1进化枝B或-C感染个体对跨越整个HIV-1蛋白质组的410个重叠肽（OLP）的组的应答。对于每种OLP，“保护率”（PR）计算为OLP无应答者和应答者之间的中位病毒载量（VL）之比。对于这两个分支，有一个负的关系之间的PR和熵的OLP序列。对有益OLP的多重反应也有显著的累加效应。对有益OLP的反应比对非有益OLP的反应具有显著更高的功能性亲和力。它们还具有上级体外抗病毒活性，重要的是，它们至少与HLA I类基因型一样预测个体的病毒载量。因此，这些数据确定了HIV的免疫原序列候选者，并提供了一种适用于其他病毒感染的T细胞免疫原设计方法。
The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.
登录
查看更多内容
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
3.1
作者：
Ali, A;Jamieson, BD;Yang, OO
通讯作者：
Yang, OO
影响因子：
30.5
作者：
Frahm, N;Kiepiela, P;Brander, C
通讯作者：
Brander, C
影响因子：
5.4
作者：
Frahm, Nicole;Yusim, Karina;Brander, Christian
通讯作者：
Brander, Christian
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.