Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants

Hong Lei, Aqu Alu, Jingyun Yang, Xi He, Cai He, Wenyan Ren, Zimin Chen, Weiqi Hong, Li Chen, Xuemei He, Li Yang, Jiong Li, Zhenling Wang, Wei Wang, Yuquan Wei, Shuaiyao Lu (), Guangwen Lu (), Xiangrong Song () and Xiawei Wei ()
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Hong Lei: West China Hospital, Sichuan University
Aqu Alu: West China Hospital, Sichuan University
Jingyun Yang: West China Hospital, Sichuan University
Xi He: West China Hospital, Sichuan University
Cai He: West China Hospital, Sichuan University
Wenyan Ren: West China Hospital, Sichuan University
Zimin Chen: West China Hospital, Sichuan University
Weiqi Hong: West China Hospital, Sichuan University
Li Chen: West China Hospital, Sichuan University
Xuemei He: West China Hospital, Sichuan University
Li Yang: West China Hospital, Sichuan University
Jiong Li: West China Hospital, Sichuan University
Zhenling Wang: West China Hospital, Sichuan University
Wei Wang: West China Hospital, Sichuan University
Yuquan Wei: West China Hospital, Sichuan University
Shuaiyao Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Guangwen Lu: West China Hospital, Sichuan University
Xiangrong Song: West China Hospital, Sichuan University
Xiawei Wei: West China Hospital, Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19.

Date: 2023
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DOI: 10.1038/s41467-023-38066-8

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