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.; 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.; Zhang, T.; Qi, H.; Guan, Y.; Xia, N.

doi:10.1101/2022.10.03.510566

bioRxiv · 10.1101/2022.10.03.510566

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.·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.·Zhang, T.·Qi, H.·Guan, Y.·Xia, N.

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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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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., 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., Zhang, T., Qi, H., Guan, Y., Xia, N.. 2022-10-03. Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response. https://doi.org/10.1101/2022.10.03.510566

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