Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Institute of Nanobiomaterials and Immunology, School of Life Sciences, Taizhou University, Taizhou 318000, China.
Department of Avian Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Poult Sci. 2023 Oct;102(10):102925. doi: 10.1016/j.psj.2023.102925. Epub 2023 Jul 6.
DNA vaccination has great potential to treat or prevent avian influenza pandemics, but the technique may be limited by low immunogenicity and gene delivery in clinical testing. Here, to improve the immune efficacy of DNA vaccines against avian influenza, we prepared and tested the immunogenicity of 4 recombinant DNA vaccines containing 2 or 3 AIV antigens. The results revealed that chickens and mice immunized with plasmid DNA containing 3 antigens (HA gene from H9N2, and NA and HA genes from H5N1) exhibited a robust immune response than chickens and mice immunized with plasmid DNAs containing 2 antigenic genes. Subsequently, this study used pβH9N1SH5 as a model antigen to study the effect of dendritic polylysine (DGL) nanoparticles as a gene delivery system and adjuvant on antigen-specific immunity in mice models. At a ratio of 1:3 DGL/pβH9N1SH5 (w/w), the pβH9N1SH5/DGL NPs showed excellent physical and chemical properties, induced higher levels of HI antibodies, and larger CD3+/CD4+ T lymphocyte and CD3+/CD8+ T lymphocyte population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2 compared with the naked pβH9N1SH5. Therefore, multiantigen gene expression methods using DGL as a delivery system may have broad application prospects in gene therapy.
DNA 疫苗在治疗或预防禽流感大流行方面具有巨大潜力，但该技术在临床测试中可能受到低免疫原性和基因传递的限制。在这里，为了提高针对禽流感的 DNA 疫苗的免疫效果，我们制备并测试了 4 种含有 2 或 3 种 AIV 抗原的重组 DNA 疫苗的免疫原性。结果表明，用含有 3 种抗原的质粒 DNA（来自 H9N2 的 HA 基因以及来自 H5N1 的 NA 和 HA 基因）免疫的鸡和小鼠比用含有 2 种抗原基因的质粒 DNA 免疫的鸡和小鼠产生了更强的免疫反应。随后，本研究使用 pβH9N1SH5 作为模型抗原，研究树突状聚赖氨酸（DGL）纳米粒作为基因传递系统和佐剂对小鼠模型中抗原特异性免疫的影响。在 DGL/pβH9N1SH5（w/w）的比例为 1:3 时，pβH9N1SH5/DGL NPs 表现出优异的物理化学性质，诱导更高水平的 HI 抗体，以及更大的 CD3+/CD4+T 淋巴细胞和 CD3+/CD8+T 淋巴细胞群体，以及细胞因子的产生，即干扰素（IFN）-γ和白细胞介素（IL）-2，与裸 pβH9N1SH5 相比。因此，使用 DGL 作为递送系统的多抗原基因表达方法在基因治疗中可能具有广阔的应用前景。
