Coping with viral diversity in HIV vaccine design.
Coping with viral diversity in HIV vaccine design.
复制标题
DOI：
10.1371/journal.pcbi.0030075
复制
发表时间：
2007-04-27
影响因子：
4.3
通讯作者：
Jojic N
中科院分区：
文献类型：
--
作者：
Nickle DC;Rolland M;Jensen MA;Pond SL;Deng W;Seligman M;Heckerman D;Mullins JI;Jojic N
人类免疫缺陷病毒1型（HIV-1）能够产生高度的遗传多样性，从而获得突变以逃避免疫压力，这造成了生产疫苗的困难。可能没有一个单一的HIV-1序列能够诱导足够广泛的免疫来抵御各种各样的感染毒株，或者在感染后阻断病毒可用的突变逃逸途径。作者描述了HIV-1免疫原的产生，该免疫原在整个已知病毒群（树的中心[COT]）中最大限度地减少了病毒株的系统发育距离，然后通过添加包括保留在其原生环境中的高频可变位点的复合序列来扩展COT免疫原。由此产生的COT+抗原将在许多独立HIV-1分离株中发现的变异压缩到适合疫苗免疫原的长度。可以将Nef蛋白中62%的变异和Gag蛋白中82%的变异捕获到三个基因长度的免疫原中。作者提出了免疫原设计，最大限度地代表了HIV-1毒株谱中存在的各种抗原特征。这些免疫原应引起针对高频病毒株以及大多数突变型病毒的免疫反应。人类免疫缺陷病毒1型（HIV-1）能够获得保持病毒活力但逃避免疫反应的突变，这是目前生产疫苗失败的原因之一。我们描述了候选HIV-1免疫原的产生，其中包括多种形式的病毒可变元件，包括一些与病毒保持共线性的元件，因此有望保留蛋白质功能。这些抗原将在许多病毒株中发现的变异压缩到适合疫苗免疫原的长度。例如，我们可以将Nef蛋白中发现的62%的变异和Gag蛋白中发现的82%的变异捕获为三个基因长度的免疫原。我们提出的免疫原设计，最大限度地代表不同的抗原特征，目前在HIV-1菌株的频谱。这些免疫原应引起针对高频病毒株以及大多数突变型病毒的免疫反应。
The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus. The ability of human immunodeficiency virus type 1 (HIV-1) to acquire mutations that preserve virus viability yet evade immune responses contributes to the current failure in producing a vaccine. We describe the generation of candidate HIV-1 immunogens that include multiple forms of variable elements of the virus including some that retain colinearity with the virus and thus are expected to retain protein function. These antigens compress the variation found in many viral strains into lengths suitable for vaccine immunogens. For example, we can capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. We put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high frequency viral strains as well as against most mutant forms of the virus.
登录
查看更多内容
影响因子：
5.4
作者：
Gao, F;Weaver, EA;Haynes, BF
通讯作者：
Haynes, BF
影响因子：
32.4
作者：
Chen, WS;Antón, LC;Yewdell, JW
通讯作者：
Yewdell, JW
影响因子：
4.4
作者：
Bartholdy, C;Stryhn, A;Thomsen, AR
通讯作者：
Thomsen, AR
DOI：
10.1084/jem.20040511
发表时间：
2004-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jones NA;Wei X;Flower DR;Wong M;Michor F;Saag MS;Hahn BH;Nowak MA;Shaw GM;Borrow P
通讯作者：
Borrow P
影响因子：
5.4
作者：
Doria-Rose, NA;Learn, GH;Mullins, JI
通讯作者：
Mullins, JI