Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response
Zhang, L.; Jiang, Y.; He, J.; Chen, J.; Qi, R.; Yuan, L.; Shao, T.; Chen, C.; Chen, Y.; Wang, X.; Lei, X.; Gao, Q.; Zhuang, C.; Zhou, M.; Ma, J.; Liu, W.; Yang, M.; Fu, R.; Wu, Y.; Chen, F.; Xiong, H.; Nie, M.; Chen, Y.; Wu, K.; Fang, M.; Wang, Y.; Zheng, Z.; Huang, S.; Ge, S.; Cheng, S.-C.; Zhu, H.; Chen, T.; Yuan, Q.; Wu, T.; Zhang, J.; Chen, Y.; Zhang, T.; Qi, H.; Guan, Y.; Xia, N.
Show abstract
The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated 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. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-{gamma}) 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.
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