Unidad de Investigación Médica Yucatán, Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico.
Virus Res. 2010 Oct;153(1):113-20. doi: 10.1016/j.virusres.2010.07.014. Epub 2010 Jul 16.
We used T cell epitope prediction tools to identify epitopes from Dengue virus polyprotein sequences, and evaluated in vivo and in vitro the immunogenicity and antigenicity of the corresponding synthetic vaccine candidates. Twenty-two epitopes were predicted to have a high affinity for MHC class I (H-2Kd, H-2Dd, H-2Ld alleles) or class II (IAd alleles). These epitopes were conserved between the four virus serotypes, but with no similarity to human and mouse sequences. Thirteen synthetic peptides induced specific antibodies production with or without T cells activation in mice. Three synthetic peptides induced mostly IgG antibodies, and one of these from the E gene induced a neutralizing response. Ten peptides induced a combination of humoral and cellular responses by CD4+ and CD8+ T cells. Twelve peptides were novel B and T cell epitopes. These results indicate that our bioinformatics strategy is a powerful tool for the identification of novel antigens and its application to human HLA may lead to a potent epitope-based vaccine against Dengue virus and many other pathogens.
我们使用 T 细胞表位预测工具来识别登革热病毒多蛋白序列中的表位，并评估相应合成候选疫苗的体内和体外免疫原性和抗原性。预测有 22 个表位对 MHC Ⅰ类（H-2Kd、H-2Dd、H-2Ld 等位基因）或Ⅱ类（IAd 等位基因）具有高亲和力。这些表位在四种病毒血清型之间具有保守性，但与人类和小鼠序列没有相似性。13 种合成肽在小鼠中诱导特异性抗体产生，无论是否激活 T 细胞。三种合成肽诱导主要产生 IgG 抗体，其中一种来自 E 基因诱导中和反应。十种肽诱导 CD4+和 CD8+T 细胞的体液和细胞应答的组合。12 种肽是新的 B 和 T 细胞表位。这些结果表明，我们的生物信息学策略是识别新抗原的有力工具，其在人类 HLA 中的应用可能导致针对登革热病毒和许多其他病原体的有效基于表位的疫苗。
