Lam Joy-Yan, Wong Wan-Man, Yuen Chun-Kit, Ng Yau-Yee, San Chun-Hin, Yuen Kwok-Yung, Kok Kin-Hang
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China.
Vaccines (Basel). 2023 Sep 29;11(10):1550. doi: 10.3390/vaccines11101550.
Developing recombinant proteins as nasal vaccines for inducing systemic and mucosal immunity against respiratory viruses is promising. However, additional adjuvants are required to overcome the low immunogenicity of protein antigens. Here, a self-adjuvanted protein-RNA ribonucleoprotein vaccine was developed and found to be an effective nasal vaccine in mice and the SARS-CoV-2 infection model. The vaccine consisted of spike RBD (as an antigen), nucleoprotein (as an adaptor), and ssRNA (as an adjuvant and RNA scaffold). This combination robustly induced mucosal IgA, neutralizing antibodies and activated multifunctional T-cells, while also providing sterilizing immunity against live virus challenge. In addition, high-resolution scRNA-seq analysis highlighted airway-resident immune cells profile during prime-boost immunization. The vaccine also possesses modularity (antigen/adaptor/RNA scaffold) and can be made to target other viruses. This protein-RNA ribonucleoprotein vaccine is a novel and promising approach for developing safe and potent nasal vaccines to combat respiratory virus infections.
开发重组蛋白作为鼻用疫苗以诱导针对呼吸道病毒的全身和黏膜免疫是很有前景的。然而，需要额外的佐剂来克服蛋白抗原免疫原性低的问题。在此，开发了一种自佐剂蛋白-RNA核糖核蛋白疫苗，并发现其在小鼠和SARS-CoV-2感染模型中是一种有效的鼻用疫苗。该疫苗由刺突RBD（作为抗原）、核蛋白（作为衔接子）和单链RNA（作为佐剂和RNA支架）组成。这种组合能强力诱导黏膜IgA、中和抗体并激活多功能T细胞，同时还能提供针对活病毒攻击的无菌免疫。此外，高分辨率单细胞RNA测序分析突出了初免-加强免疫期间气道驻留免疫细胞的特征。该疫苗还具有模块化（抗原/衔接子/RNA支架），可针对其他病毒进行制备。这种蛋白-RNA核糖核蛋白疫苗是开发安全有效的鼻用疫苗以对抗呼吸道病毒感染的一种新颖且有前景的方法。
