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树突状聚合物聚赖氨酸递送 DNA 疫苗有效增强了鸡对 H9N2 禽流感病毒感染的免疫应答。

Dendrigraft poly-L-lysines delivery of DNA vaccine effectively enhances the immunogenic responses against H9N2 avian influenza virus infection in chickens.

机构信息

Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education, Heilongjiang University, Harbin, China; Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin, China.

Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education, Heilongjiang University, Harbin, China; Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin, China; Department of Avian Infectious Disease, and Innovation Team for Pathogenic Ecology Research on Animal Influenza, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.

出版信息

Nanomedicine. 2020 Jul;27:102209. doi: 10.1016/j.nano.2020.102209. Epub 2020 Apr 16.

Abstract

Biodegradable nanomaterials can protect antigens from degradation, promote cellular absorption, and enhance immune responses. We constructed a eukaryotic plasmid [pCAGGS-opti441-hemagglutinin (HA)] by inserting the optimized HA gene fragment of H9N2 AIV into the pCAGGS vector. The pCAGGS-opti441-HA/DGL was developed through packaging the pCAGGS-opti441-HA with dendrigraft poly-l-lysines (DGLs). DGL not only protected the pCAGGS-opti441-HA from degradation, but also exhibited high transfection efficiency. Strong cellular immune responses were induced in chickens immunized with the pCAGGS-opti441-HA/DGL. The levels of IFN-γ and IL-2, and lymphocyte transformation rate of the vaccinated chickens increased at the third week post the immunization. For the vaccinated chickens, T lymphocytes were activated and proliferated, the numbers of CD3+CD4+ and CD4+/CD8+ increased, and the chickens were protected completely against H9N2 AIV challenge. This study provides a method for the development of novel AIV vaccines, and a theoretical basis for the development of safe and efficient gene delivery carriers.

摘要

可生物降解的纳米材料可以保护抗原免受降解,促进细胞吸收,并增强免疫反应。我们通过将 H9N2 AIV 的优化 HA 基因片段插入 pCAGGS 载体,构建了真核质粒 [pCAGGS-opti441-血凝素 (HA)]。通过用树枝状聚赖氨酸 (DGL) 包装 pCAGGS-opti441-HA,开发了 pCAGGS-opti441-HA/DGL。DGL 不仅可以保护 pCAGGS-opti441-HA 免受降解,而且还表现出高转染效率。用 pCAGGS-opti441-HA/DGL 免疫的鸡诱导出强烈的细胞免疫反应。免疫后第 3 周,接种鸡的 IFN-γ 和 IL-2 水平以及淋巴细胞转化率增加。对于接种疫苗的鸡,T 淋巴细胞被激活和增殖,CD3+CD4+和 CD4+/CD8+的数量增加,并且鸡完全免受 H9N2 AIV 攻击的保护。本研究为新型 AIV 疫苗的开发提供了一种方法,为安全有效的基因传递载体的开发提供了理论依据。

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