Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine
Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine
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DOI：
10.1038/sj.mt.6300036
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发表时间：
2007-02-01
影响因子：
12.4
通讯作者：
Weiner, David B.
中科院分区：
文献类型：
--
作者：
Yan, Jian;Yoon, Hanna;Weiner, David B.
人类免疫缺陷病毒（HIV）疫苗的一个重要目标是开发诱导更广泛和更有效的细胞免疫应答的免疫原。在DNA疫苗效力研究中，我们构建了一个新的B亚型env基因（EY 2 E1-B），目的是提高疫苗抗原的免疫效力。疫苗盒是基于B亚型特异性共有序列设计的，具有若干修改，包括密码子优化、RNA优化、添加Kozak序列和取代的免疫球蛋白E前导序列。缩短V1和V2环，并截断胞质尾以防止包膜再循环。用pEY 2 E1-B或单独的初级DNA免疫原pEK 2 P-B免疫三种不同品系的小鼠（BALB/c、C57 BL/6和HLA-A2转基因小鼠）三次。特异性抗体反应分析表明，EY 2 E1-B可诱导中度B亚型特异性抗体反应。此外，这种构建体在驱动细胞免疫应答方面的效力高达四倍。表位作图结果表明，由EY 2 E1-B免疫原诱导的交叉反应性细胞应答的广度和幅度增加。这些特性表明，这种合成的免疫原值得进一步研究其作为HIV疫苗混合物中的组分抗原的潜力。
An important goal for human immunodeficiency virus (HIV) vaccines is to develop immunogens that induce broader and more potent cellular immune responses. In this study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B) with the goal of increasing vaccine antigen immune potency. The vaccine cassette was designed based on subtype B-specific consensus sequence with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2 loops were shortened and the cytoplasmic tail was truncated to prevent envelope recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2 transgenic mice) were immunized three times with pEY2E1-B or the primary DNA immunogen pEK2P-B alone. The analysis of specific antibody responses suggested that EY2E1-B could induce a moderate subtype B-specific antibody response. Moreover, this construct was up to four times more potent at driving cellular immune responses. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by the EY2E1-B immunogen. These properties suggest that such a synthetic immunogen deserves further examination for its potential to serve as a component antigen in an HIV vaccine cocktail.