Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters

Liang Zhang, Yao Jiang, Jinhang He, Junyu Chen, Ruoyao Qi, Lunzhi Yuan, Tiange Shao, Hui Zhao, Congjie Chen, Yaode Chen, Xijing Wang, Xing Lei, Qingxiang Gao, Chunlan Zhuang, Ming Zhou, Jian Ma, Wei Liu, Man Yang, Rao Fu, Yangtao Wu, Feng Chen, Hualong Xiong, Meifeng Nie, Yiyi Chen, Kun Wu, Mujin Fang, Yingbin Wang, Zizheng Zheng, Shoujie Huang, Shengxiang Ge, Shih Chin Cheng, Huachen Zhu, Tong Cheng, Quan Yuan, Ting Wu (), Jun Zhang (), Yixin Chen (), Tianying Zhang (), Changgui Li (), Hai Qi (), Yi Guan () and Ningshao Xia ()
Additional contact information
Liang Zhang: Xiamen University
Yao Jiang: Xiamen University
Jinhang He: Xiamen University
Junyu Chen: Xiamen University
Ruoyao Qi: Xiamen University
Lunzhi Yuan: Xiamen University
Tiange Shao: Tsinghua University
Hui Zhao: National Institute for Food and Drug Control
Congjie Chen: Xiamen University
Yaode Chen: Xiamen University
Xijing Wang: Xiamen University
Xing Lei: Xiamen University
Qingxiang Gao: Xiamen University
Chunlan Zhuang: Xiamen University
Ming Zhou: Xiamen University
Jian Ma: Xiamen University
Wei Liu: Xiamen University
Man Yang: Xiamen University
Rao Fu: Xiamen University
Yangtao Wu: Xiamen University
Feng Chen: Xiamen University
Hualong Xiong: Xiamen University
Meifeng Nie: Xiamen University
Yiyi Chen: Xiamen University
Kun Wu: Xiamen University
Mujin Fang: Xiamen University
Yingbin Wang: Xiamen University
Zizheng Zheng: Xiamen University
Shoujie Huang: Xiamen University
Shengxiang Ge: Xiamen University
Shih Chin Cheng: Xiamen University
Huachen Zhu: The University of Hong Kong
Tong Cheng: Xiamen University
Quan Yuan: Xiamen University
Ting Wu: Xiamen University
Jun Zhang: Xiamen University
Yixin Chen: Xiamen University
Tianying Zhang: Xiamen University
Changgui Li: National Institute for Food and Drug Control
Hai Qi: Tsinghua University
Yi Guan: The University of Hong Kong
Ningshao Xia: Xiamen University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Date: 2023
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DOI: 10.1038/s41467-023-39560-9

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