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Optimization of DNA immunization against human cytomegalovirus

机译：针对人类巨细胞病毒的DNA免疫优化

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摘要

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 mug. Go-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.
机译：分别注射表达全长膜锚定或分泌形式的人巨细胞病毒（HCMV）-糖蛋白B（gB）的质粒VR-gB和VR-gB Delta tm的小鼠的免疫应答，以及表达该蛋白的VR-pp65分析了HCMV-磷酸蛋白65（pp65）。用局麻药布比卡因对小鼠进行预处理不会增强抗体的产生，并且与免疫质粒共表达的IFN-α会引起抗体反应的适度增加。但是，在四头肌的三个部位接种的小鼠的抗体应答要比在相同剂量和相同肌肉的一个部位接种的小鼠的抗体应答更高。与表达膜锚定形式的gB的构建体相比，pVR-gB Delta tm诱导的抗体效价显着更高，用pVR-gB Delta tm引发，然后用gB亚基加强免疫可产生高滴度的抗体反应。在约50％的小鼠中，用VR-pp65免疫可诱导约50％的小鼠剂量依赖性CTL反应。 IFN-α的Go表达并不影响反应小鼠的数量。这些发现对于优化DNA疫苗接种后对HCMV的体液和细胞免疫反应可能很重要。

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