André S, Seed B, Eberle J, Schraut W, Bültmann A, Haas J
Max-von-Pettenkofer Institut, Genzentrum, Universität München, Munich, Germany.
J Virol. 1998 Feb;72(2):1497-503. doi: 10.1128/JVI.72.2.1497-1503.1998.
DNA vaccination elicits humoral and cellular immune responses and has been shown to confer protection against several viral, bacterial, and parasitic pathogens. Here we report that optimized codon usage of an injected DNA sequence considerably increases both humoral and cellular immune responses. We recently generated a synthetic human immunodeficiency virus type 1 gp120 sequence in which most wild-type codons were replaced with codons from highly expressed human genes (syngp120). In vitro expression of syngp120 is considerably increased in comparison to that of the respective wild-type sequence. In BALB/c mice, DNA immunization with syngp120 resulted in significantly increased antibody titers and cytotoxic T-lymphocyte reactivity, suggesting a direct correlation between expression levels and the immune response. Moreover, syngp120 is characterized by rev-independent expression and a low risk of recombination with viral sequences. Thus, synthetic genes with optimized codon usage represent a novel strategy to increase the efficacy and safety of DNA vaccination.
DNA疫苗接种可引发体液免疫和细胞免疫反应，并且已证明能提供针对多种病毒、细菌和寄生虫病原体的保护作用。在此我们报告，注射的DNA序列的密码子使用优化可显著增强体液免疫和细胞免疫反应。我们最近构建了一个合成的人类免疫缺陷病毒1型gp120序列，其中大多数野生型密码子被来自高表达人类基因的密码子所取代（合成gp120）。与相应的野生型序列相比，合成gp120的体外表达显著增加。在BALB/c小鼠中，用合成gp120进行DNA免疫导致抗体滴度和细胞毒性T淋巴细胞反应性显著增加，表明表达水平与免疫反应之间存在直接关联。此外，合成gp120的特征在于不依赖于Rev的表达以及与病毒序列重组的风险较低。因此，具有优化密码子使用的合成基因代表了一种提高DNA疫苗接种效力和安全性的新策略。
