Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters
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Published:2023-07-11
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Zhang LiangORCID, Jiang Yao, He Jinhang, Chen Junyu, Qi Ruoyao, Yuan Lunzhi, Shao Tiange, Zhao Hui, Chen Congjie, Chen Yaode, Wang Xijing, Lei Xing, Gao QingxiangORCID, Zhuang Chunlan, Zhou Ming, Ma Jian, Liu Wei, Yang Man, Fu Rao, Wu Yangtao, Chen Feng, Xiong Hualong, Nie Meifeng, Chen Yiyi, Wu Kun, Fang Mujin, Wang Yingbin, Zheng ZizhengORCID, Huang Shoujie, Ge ShengxiangORCID, Cheng Shih ChinORCID, Zhu HuachenORCID, Cheng TongORCID, Yuan QuanORCID, Wu Ting, Zhang JunORCID, Chen YixinORCID, Zhang TianyingORCID, Li Changgui, Qi HaiORCID, Guan Yi, Xia NingshaoORCID
Abstract
AbstractThe 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.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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