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编码单纯疱疹病毒2型糖蛋白B和糖蛋白D嵌合蛋白的DNA质粒的免疫学特性

Immunological properties of a DNA plasmid encoding a chimeric protein of herpes simplex virus type 2 glycoprotein B and glycoprotein D.

作者信息

Domingo C, Gadea I, Pardeiro M, Castilla C, Fernández S, Fernández-Clua M A, De la Cruz Troca J J, Punzón C, Soriano F, Fresno M, Tabarés E

机构信息

Departamento de Medicina Preventiva y Salud Pública (Microbiología), Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.

出版信息

Vaccine. 2003 Sep 8;21(25-26):3565-74. doi: 10.1016/s0264-410x(03)00423-7.

Abstract

A DNA plasmid containing a chimeric sequence encoding both herpes simplex virus type 2 (HSV-2) glycoprotein B (gB) and glycoprotein D (gD) external domains (pcgDB) was used to immunize BALB/c mice against genital HSV-2 infection. To determine the efficacy of this vaccine, groups of mice immunized with the pcgDB plasmid were compared with animals immunized with plasmids corresponding to the individual proteins (pcgBt or pcgDt), administered separately or in combination (pcgBt + pcgDt). We studied the response of the different mouse groups to viral challenge by analyzing clinical disease (vaginitis), serum antibody levels, as well as lymphoproliferative responses and cytokine production by spleen cells. Increased IFN-gamma levels correlated with prolonged survival in mice immunized with the plasmid pcgDB, relative to mice immunized with plasmids coding for the individual proteins alone or in combination. Our results show that immunization with the plasmid encoding the chimeric protein is advantageous over separate proteins. These findings may have important implications for the development of multivalent DNA vaccines against HSV and other complex pathogens.

摘要

一种含有编码单纯疱疹病毒2型(HSV-2)糖蛋白B(gB)和糖蛋白D(gD)胞外结构域的嵌合序列的DNA质粒(pcgDB),被用于免疫BALB/c小鼠以预防生殖器HSV-2感染。为了确定该疫苗的效力,将用pcgDB质粒免疫的小鼠组与用对应单个蛋白的质粒(pcgBt或pcgDt)免疫的动物进行比较,这些单个蛋白质粒单独或联合(pcgBt + pcgDt)给药。我们通过分析临床疾病(阴道炎)、血清抗体水平以及脾细胞的淋巴细胞增殖反应和细胞因子产生,研究了不同小鼠组对病毒攻击的反应。相对于用编码单个蛋白的质粒单独或联合免疫的小鼠,用质粒pcgDB免疫的小鼠中,干扰素-γ水平升高与生存期延长相关。我们的结果表明,用编码嵌合蛋白的质粒免疫比单独使用单个蛋白具有优势。这些发现可能对开发针对HSV和其他复杂病原体的多价DNA疫苗具有重要意义。

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