VP22蛋白对炭疽DNA疫苗增强作用的评价

Stuart D Perkins, Helen C Flick-Smith, Helen S Garmory, Angela E Essex-Lopresti, Freda K Stevenson, Robert J Phillpotts
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引用次数: 11

摘要

背景:以前,为了提高疗效,从DNA疫苗中表达的抗原已与来自I型单纯疱疹病毒的VP22蛋白融合。然而,VP22的免疫增强机制尚不清楚,最初认为VP22可以介导细胞间传播的观点也受到质疑。尽管如此,VP22与DNA疫苗中表达的抗原的融合改善了免疫反应,特别是对非分泌抗原。方法:本研究将VP22蛋白基因与炭疽杆菌保护性抗原(PA)基因融合。对炭疽芽孢杆菌感染的保护性免疫几乎完全基于对PA的应答,我们已经产生了两种结构,其中VP22融合到63 kDa蛋白酶裂解的PA片段(PA63)的N端或c端。结果:用这些构建物对A/J小鼠进行基因枪免疫后,我们观察到抗pa抗体反应没有改善。在用70 - 50%致死剂量的炭疽杆菌STI孢子腹腔攻击后,用表达PA63的DNA疫苗和表达PA63与VP22融合蛋白的DNA疫苗免疫的组在保护作用上没有明显差异。结论:表达PA63的DNA疫苗免疫A/J小鼠后,VP22融合并没有提高对活孢子攻击的保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.

Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.

Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.

Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.

BACKGROUND: Previously, antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy. However, the immune enhancing mechanism of VP22 is poorly understood and initial suggestions that VP22 can mediate intercellular spread have been questioned. Despite this, fusion of VP22 to antigens expressed from DNA vaccines has improved immune responses, particularly to non-secreted antigens. METHODS: In this study, we fused the gene for the VP22 protein to the gene for Protective Antigen (PA) from Bacillus anthracis, the causative agent of anthrax. Protective immunity against infection with B. anthracis is almost entirely based on a response to PA and we have generated two constructs, where VP22 is fused to either the N- or the C-terminus of the 63 kDa protease-cleaved fragment of PA (PA63). RESULTS: Following gene gun immunisation of A/J mice with these constructs, we observed no improvement in the anti-PA antibody response generated. Following an intraperitoneal challenge with 70 50% lethal doses of B. anthracis strain STI spores, no difference in protection was evident in groups immunised with the DNA vaccine expressing PA63 and the DNA vaccines expressing fusion proteins of PA63 with VP22. CONCLUSION: VP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA63.

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