Shell-mediated phagocytosis to reshape viral-vectored vaccine-induced immunity
Shell-mediated phagocytosis to reshape viral-vectored vaccine-induced immunity
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DOI：
10.1016/j.biomaterials.2021.121062
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发表时间：
2021-08-18
期刊：
影响因子：
14
通讯作者：
Sun, Caijun
中科院分区：
文献类型：
--
作者：
Feng, Fengling;Hao, Haibin;Sun, Caijun
腺病毒（Adenovirus，Ad）作为基因载体得到了广泛的应用，但系统免疫引起的副作用仍是其临床应用的主要障碍。无针粘膜免疫与广告为基础的疫苗显示出优势，但仍然面临着不良的粘膜反应。我们在此报告，化学工程的单一活病毒为基础的疫苗有效地调制的位置和模式，随后引发的免疫。通过将功能材料精确地组装到单个活Ad颗粒上，修饰的病毒以吞噬依赖的方式进入宿主细胞，这与天然Ad的受体介导的进入完全不同。RNA-Seq结果进一步证明，修饰后的Ad通过吞噬相关途径诱导的先天免疫发生了急剧的改变，从而促进了抗原呈递细胞（APC）的活化和成熟。此外，功能性外壳使修饰的基于Ad的载体与小鼠鼻组织的粘膜粘附增强，然后延长在粘膜表面上的停留时间，导致在局部甚至远程粘膜相关淋巴组织中的强大的粘膜伊加产生和T细胞免疫。本研究表明，化学工程方法可以很好地调控疫苗诱导的免疫应答，为针对多种新发传染病的无针黏膜靶向疫苗的设计提供了理论依据。
Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.