Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins
Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins
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DOI：
10.1016/j.virol.2006.10.017
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发表时间：
2007-03-30
期刊：
影响因子：
3.7
通讯作者：
Hahn, Beatrice H.
中科院分区：
文献类型：
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作者：
Kothe, Denise L.;Decker, Julie M.;Hahn, Beatrice H.
“集中”（祖先和共识）HIV-1包膜免疫原在实验动物中诱导广泛的交叉反应性T细胞反应；然而，它们引发交叉反应中和抗体的潜力尚未得到充分探索。在这里，我们报告了一组共有亚型 B (ConB) 包膜的构建，并将其生物学、抗原性和免疫原性特性与来自早期和急性 HIV-1 感染个体的两种野生型包膜对照进行比较。 ConB env 基因的全长 (gp160)、未切割 (gp160-UNC)、截短 (gp145) 和 N 连接糖基化位点删除 (gp160-201N/S) 版本表达的糖蛋白被包装到病毒颗粒中，并且除了融合缺陷型 gp160-LTNC 之外，通过 CCR5 共受体介导感染。含有ConB Envs的假病毒粒子对患者血浆和单克隆抗体的中和反应敏感，表明在当代B亚型病毒中发现的中和表位得以保留。当在豚鼠中用作 DNA 疫苗时，Con13 和野生型 env 免疫原诱导了明显的结合，但总体上仅产生低水平的中和抗体。然而，所有四种Con13免疫原在引发针对一组1级和2级病毒的中和抗体方面均明显比一种野生型疫苗更有效，并且ConB gp145和gp160在诱导针对1级病毒的中和抗体方面明显比两种野生型疫苗更有效。因此，共有亚型B env免疫原在诱导中和抗体应答方面似乎至少与野生型B env免疫原一样好，并且在某些情况下优于野生型B env免疫原，并且可以通过特定基因修饰进一步改进。 (c) 2006 Elsevier Inc. 保留所有权利。
"Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic proper-ties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-LTNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, Con13 and wild-type env immumogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four Con13 immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications. (c) 2006 Elsevier Inc. All rights reserved.