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针对人巨细胞病毒的DNA免疫优化

Optimization of DNA immunization against human cytomegalovirus.

作者信息

Endrész V, Burián K, Berencsi K, Gyulai Z, Kari L, Horton H, Virok D, Méric C, Plotkin S A, Gönczöl E

机构信息

Department of Medical Microbiology, University of Szeged, Szeged, Hungary.

出版信息

Vaccine. 2001 Jul 16;19(28-29):3972-80. doi: 10.1016/s0264-410x(01)00116-5.

DOI:10.1016/s0264-410x(01)00116-5
PMID:11427273
Abstract

The immune responses of mice injected with plasmids VR-gB and VR-gB Delta tm expressing the full-length membrane-anchored, or secreted forms of human cytomegalovirus (HCMV)-glycoprotein B (gB), respectively, and VR-pp65 expressing the HCMV-phosphoprotein 65 (pp65) were analyzed. Pretreatment of mice with the local anesthetic bupivacaine did not enhance antibody production, and IFN-alpha co-expressed with the immunizing plasmids induced a moderate increase in the antibody response. However, antibody response was higher in mice inoculated at three sites in the musculus quadriceps than in mice inoculated at one site with the same dose and in the same muscle. pVR-gB Delta tm induced significantly higher antibody titers than the construct expressing the membrane-anchored form of gB, and priming with pVR-gB Delta tm followed by boosting with the gB subunit resulted in high-titer antibody responses. Immunization with VR-pp65 induced dose-dependent CTL responses in about 50% of the mice at a dose of 50 microg. Co-expression of IFN-alpha did not affect the number of responding mice. These findings might be important for optimization of humoral and cellular immune responses to HCMV after DNA vaccination.

摘要

分析了分别注射表达人巨细胞病毒(HCMV)糖蛋白B(gB)全长膜锚定形式或分泌形式的质粒VR - gB和VR - gB Delta tm,以及表达HCMV磷蛋白65(pp65)的VR - pp65后小鼠的免疫反应。用局部麻醉药布比卡因预处理小鼠并未增强抗体产生,与免疫质粒共表达的IFN -α诱导抗体反应适度增加。然而,在股四头肌三个部位接种的小鼠的抗体反应高于在同一剂量和同一肌肉的一个部位接种的小鼠。pVR - gB Delta tm诱导的抗体滴度明显高于表达gB膜锚定形式的构建体,先用pVR - gB Delta tm进行初次免疫,然后用gB亚基进行加强免疫,可产生高滴度抗体反应。以50μg的剂量用VR - pp65免疫在约50%的小鼠中诱导了剂量依赖性CTL反应。IFN -α的共表达不影响反应小鼠的数量。这些发现对于DNA疫苗接种后优化针对HCMV的体液和细胞免疫反应可能很重要。

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