Novel AAV-based genetic vaccines encoding truncated dengue virus envelope proteins elicit humoral immune responses in mice
Novel AAV-based genetic vaccines encoding truncated dengue virus envelope proteins elicit humoral immune responses in mice
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DOI：
10.1016/j.micinf.2012.05.002
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发表时间：
2012-09-01
影响因子：
5.8
通讯作者：
Wang, Lili
中科院分区：
文献类型：
--
作者：
Li, Xueling;Cao, Hong;Wang, Lili
登革病毒的包膜蛋白参与宿主细胞附着，进入并诱导保护性免疫。目前的工作重点是通过混合四种单价疫苗成分来生产四价疫苗。在这项工作中，我们开发了一种基于表达登革热病毒羧基末端截断包膜蛋白（79E）的新型腺相关病毒（AAV）载体的遗传疫苗。Western blot证实重组蛋白79E在HEK 293细胞中的表达。将新型AAV衣壳（AAV2/8或AAV2/rh32.33）包装的载体肌注于C57BL/6小鼠。在小鼠体内产生登革病毒抗原，并诱导免疫20周后仍可检测到的针对登革病毒的持久抗体反应。AAV2/8疫苗诱导的抗登革病毒抗体水平高于AAV2/rh32.33疫苗或AAV质粒。此外，抗登革热抗体可以中和同质登革热病毒。结果表明，AAV疫苗具有良好的免疫原性，可用于研制有效的登革热疫苗。(C) 2012巴斯德研究所。Elsevier Masson SAS出版。版权所有。
The envelope protein of dengue virus is involved in host cell attachment for entry and induction of protective immunity. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we developed a genetic vaccine based on a novel adeno-associated viral (AAV) vector expressing the carboxy-terminal truncated envelope protein (79E) of dengue virus. The expression of the recombinant 79E protein in HEK 293 cells was confirmed by Western blot. Vectors packaged with novel AAV capsids (AAV2/8 or AAV2/rh32.33) were injected into C57BL/6 mice intramuscularly. Dengue virus antigen was produced in the mice and induced long-lasting antibody responses against the dengue virus still detectable 20 weeks after immunization. AAV2/8 vaccine induced higher anti-dengue virus antibody levels than AAV2/rh32.33 vaccine or AAV plasmid. Furthermore, the anti-dengue antibodies could neutralize homogeneous dengue virus. These results demonstrated that the AAV vaccines possessed appropriate immunogenicity and could be used for the development of an effective dengue vaccine. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.