Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou Key Laboratory of Biomedicine and Advanced Dosage Forms, School of Life Sciences, Taizhou University, Zhejiang, Taizhou 318000, China; Zhejiang-Malaysia Joint Laboratory for Bioactive Materials and Applied Microbiology, School of Life Sciences, Taizhou University, Zhejiang, Taizhou 318000, China.
Department of Avian Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education, Heilongjiang University, Harbin 150500, China; Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Sciences, Heilongjiang University, Heilongjiang Harbin 150080, China.
Int J Biol Macromol. 2023 Nov 1;251:126286. doi: 10.1016/j.ijbiomac.2023.126286. Epub 2023 Aug 12.
H7 avian influenza virus has caused multiple human infections and poses a severe public health threat. In response to the highly variable nature of AIVs, a novel, easily regenerated DNA vaccine has great potential in treating or preventing avian influenza pandemics. Nevertheless, DNA vaccines have many disadvantages, such as weak immunogenicity and poor in vivo delivery. To further characterize and solve these issues and develop a novel H7 AIV DNA vaccine with enhanced stability and immunogenicity, we constructed nine AIV DNA plasmids, and the immunogenicity screened showed that mice immunized with pβH7N2SH9 elicited stronger hemagglutination-inhibiting (HI) antibodies than other eight plasmid DNAs. Then, to address the susceptibility to degradation and low transfection rate of DNA vaccine in vivo, we developed pβH7N2SH9/DGL NPs by encapsulating the pβH7N2SH9 within the dendrigraft poly-l-lysines nanoparticles. As expected, these NPs exhibited excellent physical and chemical properties, were capable of promote lymphocyte proliferation, and induce stronger humoral and cellular responses than the naked pβH7N2SH9, including higher levels of HI antibodies than naked pβH7N2SH9, as well as the production of cytokines, namely, IL-2, IFN-α. Taken together, our results suggest that the construction of an immune-enhanced H7-AIV DNA nanovaccine may be a promising strategy against most influenza viruses.
H7 禽流感病毒已导致多次人类感染，并对公共卫生构成严重威胁。针对 AIVs 的高度变异性，新型、易于再生的 DNA 疫苗在治疗或预防禽流感大流行方面具有巨大潜力。然而，DNA 疫苗存在免疫原性弱、体内递送效果差等诸多缺点。为了进一步阐明和解决这些问题，并开发一种新型 H7 AIV DNA 疫苗，提高其稳定性和免疫原性，我们构建了 9 种 AIV DNA 质粒，并对其免疫原性进行筛选，结果显示，用 pβH7N2SH9 免疫的小鼠诱导产生了更强的血凝抑制（HI）抗体，优于其他 8 种质粒 DNA。接着，为了解决 DNA 疫苗在体内易降解和转染率低的问题，我们通过将 pβH7N2SH9 包裹在树枝状大分子聚赖氨酸纳米颗粒内，构建了 pβH7N2SH9/DGL NPs。正如预期的那样，这些 NPs 表现出了优异的物理化学性质，能够促进淋巴细胞增殖，并诱导比裸质粒 pβH7N2SH9 更强的体液和细胞反应，包括比裸质粒 pβH7N2SH9 更高水平的 HI 抗体，以及细胞因子的产生，如 IL-2、IFN-α。总之，我们的研究结果表明，构建免疫增强型 H7-AIV DNA 纳米疫苗可能是一种针对大多数流感病毒的有前途的策略。
