School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; Longhu Laboratory of Advanced Immunology, Zhengzhou 450046, China; Henan Key Laboratory of Immunobiology, Zhengzhou 450001, China.
Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China.
Carbohydr Polym. 2024 Mar 15;328:121689. doi: 10.1016/j.carbpol.2023.121689. Epub 2023 Dec 16.
Influenza A virus (IAV) poses a significant threat to human and animal health, necessitating the development of universal influenza vaccines that can effectively activate mucosal immunity. Intranasal immunization has attracted significant attention due to its capacity to induce triple immune responses, including mucosal secretory IgA. However, inducing mucosal immunity through vaccination is challenging due to the self-cleansing nature of the mucosal surface. Thiolated chitosan (TCS) were explored for mucosal vaccine delivery, capitalizing on biocompatibility and bioadhesive properties of chitosan, with thiol modification enhancing mucoadhesive capability. The focus was on developing a universal nanovaccine by utilizing TCS-encapsulated virus-like particles displaying conserved B-cell and T-cell epitopes from M2e and NP proteins of IAV. The optimal conditions for nanoparticle formation were investigated by adjusting the thiol groups content of TCS and the amount of sodium tripolyphosphate. The nanovaccine induced robust immune responses and provided complete protection against IAVs from different species following intranasal immunization. The broad protective effect of nanovaccines can be attributed to the synergistic effect of antibodies and T cells. This study developed a universal intranasal nanovaccine and demonstrated the potential of TCS in the development of mucosal vaccines for respiratory infectious diseases.
甲型流感病毒(IAV)对人类和动物的健康构成重大威胁,因此需要开发能够有效激活黏膜免疫的通用流感疫苗。鼻内免疫因其能够诱导三重免疫反应,包括黏膜分泌型 IgA,而受到广泛关注。然而,由于黏膜表面的自我清洁特性,通过疫苗接种诱导黏膜免疫具有挑战性。巯基化壳聚糖(TCS)被探索用于黏膜疫苗传递,利用壳聚糖的生物相容性和生物黏附特性,硫醇修饰增强了黏膜黏附能力。研究的重点是利用 TCS 包封的展示 IAV M2e 和 NP 蛋白保守 B 细胞和 T 细胞表位的病毒样颗粒,开发通用纳米疫苗。通过调整 TCS 的巯基含量和三聚磷酸钠的用量,研究了纳米颗粒形成的最佳条件。鼻内免疫后,纳米疫苗诱导了强烈的免疫反应,并为不同物种的 IAV 提供了完全保护。纳米疫苗的广泛保护作用可归因于抗体和 T 细胞的协同作用。本研究开发了一种通用的鼻内纳米疫苗,并证明了 TCS 在开发针对呼吸道传染病的黏膜疫苗方面的潜力。
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