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; Ningshao Xia

doi:10.1038/s41467-023-39560-9

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

Nat Commun. 2023 Jul 11;14(1):4117. doi: 10.1038/s41467-023-39560-9.

Authors

Liang Zhang^#¹, Yao Jiang^#¹, Jinhang He^#¹, Junyu Chen^#¹, Ruoyao Qi^#¹, Lunzhi Yuan^#¹, Tiange Shao^#², Hui Zhao^#³, Congjie Chen¹, Yaode Chen¹, Xijing Wang¹, Xing Lei¹, Qingxiang Gao⁴, Chunlan Zhuang¹, Ming Zhou¹, Jian Ma¹, Wei Liu¹, Man Yang¹, Rao Fu¹, Yangtao Wu¹, Feng Chen¹, Hualong Xiong¹, Meifeng Nie¹, Yiyi Chen¹, Kun Wu¹, Mujin Fang^{1

5}, Yingbin Wang^{1

5}, Zizheng Zheng^{1

5}, Shoujie Huang^{1

5}, Shengxiang Ge^{1

5}, Shih Chin Cheng⁴, Huachen Zhu^{6

7}, Tong Cheng^{1

5}, Quan Yuan^{1

5}, Ting Wu^{8

9}, Jun Zhang^{10

11}, Yixin Chen^{12

13}, Tianying Zhang^{14

15}, Changgui Li¹⁶, Hai Qi¹⁷, Yi Guan^{18

19}, Ningshao Xia^{20

21}

Affiliations

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China.
² Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, 100084, Beijing, China.
³ National Institute for Food and Drug Control, 102629, Beijing, China.
⁴ State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China.
⁵ Xiang An Biomedicine Laboratory, 361102, Xiamen, Fujian, China.
⁶ State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China.
⁷ Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (STU/HKU), Shantou University, 515063, Shantou, China.
⁸ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China. wuting@xmu.edu.cn.
⁹ Xiang An Biomedicine Laboratory, 361102, Xiamen, Fujian, China. wuting@xmu.edu.cn.
¹⁰ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China. zhangj@xmu.edu.cn.
¹¹ Xiang An Biomedicine Laboratory, 361102, Xiamen, Fujian, China. zhangj@xmu.edu.cn.
¹² State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China. yxchen2008@xmu.edu.cn.
¹³ Xiang An Biomedicine Laboratory, 361102, Xiamen, Fujian, China. yxchen2008@xmu.edu.cn.
¹⁴ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China. zhangtianying@xmu.edu.cn.
¹⁵ Xiang An Biomedicine Laboratory, 361102, Xiamen, Fujian, China. zhangtianying@xmu.edu.cn.
¹⁶ National Institute for Food and Drug Control, 102629, Beijing, China. changguili@aliyun.com.
¹⁷ Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, 100084, Beijing, China. qihai@tsinghua.edu.cn.
¹⁸ State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China. yguan@hku.hk.
¹⁹ Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (STU/HKU), Shantou University, 515063, Shantou, China. yguan@hku.hk.
²⁰ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China. nsxia@xmu.edu.cn.
²¹ Xiang An Biomedicine Laboratory, 361102, Xiamen, Fujian, China. nsxia@xmu.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19 Vaccines
COVID-19* / prevention & control
Cricetinae
Humans
Influenza Vaccines*
Influenza, Human*
SARS-CoV-2

Substances

COVID-19 Vaccines
Influenza Vaccines

Supplementary concepts

SARS-CoV-2 variants