Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type I group m consensus envelope glycoprotein
Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type I group m consensus envelope glycoprotein
复制标题
DOI：
10.1128/jvi.79.2.1154-1163.2005
复制
发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Haynes, BF
中科院分区：
文献类型：
--
作者：
Gao, F;Weaver, EA;Haynes, BF
人类免疫缺陷病毒（HIV-1）的遗传变异是艾滋病疫苗开发的主要障碍。为了减少候选免疫原与野毒株之间的遗传距离，我们设计并合成了与当代HIV-1亚型和重组体等距离的人工M组共有env基因（CON 6基因）。这种新的包膜基因表达结合可溶性CD 4的糖蛋白，利用CCR 5而不是CXCR 4作为辅助受体，并介导HIV-1进入。关键的线性、构象和聚糖依赖性单克隆抗体表位保留在CON 6中，并且该糖蛋白同样被来自感染不同HIV-1亚型的个体的血清识别。当在BALB/c小鼠中用作DNA疫苗，随后是重组牛痘病毒加强时，CON 6 env gp 120和gp 140 CF引起产生γ干扰素的T细胞应答，其识别来自三种HIV-1 Env蛋白CON 6、MN（亚型13）和Chn 19（亚型C）的重叠肽池内的表位。用重组CON 6 Env gp 120和gp 140 CF糖蛋白免疫的豚鼠血清弱中和选定的HIV-1原代分离株。因此，计算机生成的“共有”env基因能够表达保留野生型HIV-1包膜的结构、功能和免疫原性特性的包膜糖蛋白。
Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 subtypes. When used as a DNA vaccine followed by a recombinant vaccinia virus boost in BALB/c mice, CON6 env gp120 and gp140CF elicited gamma interferon-producing T-cell responses that recognized epitopes within overlapping peptide pools from three HIV-1 Env proteins, CON6, MN (subtype 13), and Chn19 (subtype C). Sera from guinea pigs immunized with recombinant CON6 Env gp120 and gp140CF glycoproteins weakly neutralized selected HIV-1 primary isolates. Thus, the computer-generated "consensus" env genes are capable of expressing envelope glycoproteins that retain the structural, functional, and immunogenic properties of wild-type HIV-1 envelopes.