Tian Yu, Hu Lijia, Huang Qingrui, Qi Jinming, Shen Lijuan, Wang Guosheng, Yu Weili, Hu Tao
College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
School of International Relations, Beijing Language and Culture University, Beijing 100083, China.
Int J Biol Macromol. 2025 Mar;294:139395. doi: 10.1016/j.ijbiomac.2024.139395. Epub 2025 Jan 3.
SARS-CoV-2 has the characteristics of strong transmission with severe morbidity and mortality. Protein-based vaccines have the properties of specificity, effectiveness and safety against SARS-CoV-2. Receptor-binding domain (RBD) homotrimer affords high protection efficacy against stringent lethal viral challenge. Mucosal immunity could block the infection that first infect and replicate in the upper airway mucosa. Due to the physical barriers of the mucosa, mucosal vaccines necessitated appropriate adjuvants and delivery system. In the present study, maltodextrin, PEI and 2',3'-cGAMP acted as the mucosal adjuvants and RBD trimer as the antigen. A mucosal nanovaccine was prepared by assembly of adjuvants and the antigen to a nanoparticle. The vaccine elicited strong serum RBD-specific IgG and IgA response, and mild mucosal IgA and IgG response in the respiratory tract. It stimulated strong neutralizing antibody response and high ACE2-blocking activity in the sera. It promoted the RBD-specific CD4 and CD8 T cells secreting IFN-γ, IL-4 and IL-17 A. Moreover, it elicited durable RBD-specific memory T and B memory cell response, activated the T and B cells, enhanced the cytotoxic T cell killing effect, and promoted the maturation of DCs. These findings suggested the clinical potential of the vaccine to combat against SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有传播力强、发病率和死亡率高的特点。基于蛋白质的疫苗对SARS-CoV-2具有特异性、有效性和安全性。受体结合域（RBD）三聚体对严格致死性病毒攻击具有高保护效力。黏膜免疫可阻断在上呼吸道黏膜首先感染和复制的感染。由于黏膜的物理屏障，黏膜疫苗需要合适的佐剂和递送系统。在本研究中，麦芽糖糊精、聚乙烯亚胺（PEI）和2',3'-环状二核苷酸单磷酸腺苷（2',3'-cGAMP）作为黏膜佐剂，RBD三聚体作为抗原。通过将佐剂和抗原组装成纳米颗粒制备了一种黏膜纳米疫苗。该疫苗在血清中引发了强烈的RBD特异性IgG和IgA反应，在呼吸道中引发了轻度的黏膜IgA和IgG反应。它在血清中刺激了强烈的中和抗体反应和高血管紧张素转换酶2（ACE2）阻断活性。它促进了RBD特异性CD4和CD8 T细胞分泌γ干扰素、白细胞介素-4和白细胞介素-17A。此外，它引发了持久的RBD特异性记忆T细胞和B记忆细胞反应，激活了T细胞和B细胞，增强了细胞毒性T细胞的杀伤作用，并促进了树突状细胞（DC）的成熟。这些发现表明该疫苗在对抗SARS-CoV-2感染方面具有临床潜力。
