An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters

Shaofeng Deng, Ying Liu, Rachel Chun-Yee Tam, Pin Chen, Anna Jinxia Zhang, Bobo Wing-Yee Mok, Teng Long, Anja Kukic, Runhong Zhou, Haoran Xu, Wenjun Song, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Zhiwei Chen, Kwok-Yung Yuen, Pui Wang () and Honglin Chen ()
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Shaofeng Deng: the University of Hong Kong
Ying Liu: the University of Hong Kong
Rachel Chun-Yee Tam: the University of Hong Kong
Pin Chen: the University of Hong Kong
Anna Jinxia Zhang: the University of Hong Kong
Bobo Wing-Yee Mok: the University of Hong Kong
Teng Long: the University of Hong Kong
Anja Kukic: the University of Hong Kong
Runhong Zhou: the University of Hong Kong
Haoran Xu: the University of Hong Kong
Wenjun Song: the University of Hong Kong
Jasper Fuk-Woo Chan: the University of Hong Kong
Kelvin Kai-Wang To: the University of Hong Kong
Zhiwei Chen: the University of Hong Kong
Kwok-Yung Yuen: the University of Hong Kong
Pui Wang: the University of Hong Kong
Honglin Chen: the University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.

Date: 2023
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DOI: 10.1038/s41467-023-37697-1

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