A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection

Chen, J.; Wang, P.; Yuan, L.; Zhang, L.; Zhao, H.; Chen, C.; Chen, Y.; Han, J.; Jia, J.; Lu, Z.; Hong, J.; Chen, L.; Fan, C.; Wang, Q.; Chen, R.; Cai, M.; Qi, R.; Wang, X.; Ma, J.; Zhou, M.; Yu, H.; Zhuang, C.; Liu, X.; Han, Q.; Wang, G.; Su, Y.; Yuan, Q.; Cheng, T.; Wu, T.; Ye, X.; Li, C.; Zhang, T.; Zhang, J.; Zhu, H.; Chen, H.; Xia, N.

doi:10.1101/2021.11.13.468472

bioRxiv · 10.1101/2021.11.13.468472

A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection

Chen, J.·Wang, P.·Yuan, L.·Zhang, L.·Zhao, H.·Chen, C.·Chen, Y.·Han, J.·Jia, J.·Lu, Z.·Hong, J.·Chen, L.·Fan, C.·Wang, Q.·Chen, R.·Cai, M.·Qi, R.·Wang, X.·Ma, J.·Zhou, M.·Yu, H.·Zhuang, C.·Liu, X.·Han, Q.·Wang, G.·Su, Y.·Yuan, Q.·Cheng, T.·Wu, T.·Ye, X.·Li, C.·Zhang, T.·Zhang, J.·Zhu, H.·Chen, H.·Xia, N.

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Abstract

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

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Chen, J., Wang, P., Yuan, L., Zhang, L., Zhao, H., Chen, C., Chen, Y., Han, J., Jia, J., Lu, Z., Hong, J., Chen, L., Fan, C., Wang, Q., Chen, R., Cai, M., Qi, R., Wang, X., Ma, J., Zhou, M., Yu, H., Zhuang, C., Liu, X., Han, Q., Wang, G., Su, Y., Yuan, Q., Cheng, T., Wu, T., Ye, X., Li, C., Zhang, T., Zhang, J., Zhu, H., Chen, H., Xia, N.. 2021-11-15. A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection. https://doi.org/10.1101/2021.11.13.468472

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