Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination

Zhou, R.; Wang, P.; Wong, Y.-C.; Xu, H.; Lau, S.-Y.; Liu, L.; Mok, B. W.-Y.; Peng, Q.; Liu, N.; Deng, S.; Tam, R. C.-Y.; Huang, H.; Zhang, A. J.; Zhou, D.; Zhou, B.; Chan, C.-Y.; Du, Z.; Yang, D.; Au, K.-K.; Yuen, K.-Y.; Chen, H.; Chen, Z.

doi:10.1101/2021.10.21.465252

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bioRxiv · 10.1101/2021.10.21.465252

Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination

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Abstract

BackgroundVaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. MethodsSince mucosal immunity is critical for nasal prevention, we investigated an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FindingsSubstantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. InterpretationOur results demonstrated that intranasal influenza-based boost vaccination is required for inducing mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FundingThis study was supported by the Research Grants Council Collaborative Research Fund (C7156-20G, C1134-20G and C5110-20G), General Research Fund (17107019) and Health and Medical Research Fund (19181052 and 19181012) in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program (JSGG20200225151410198); the Health@InnoHK, Innovation and Technology Commission of Hong Kong; and National Program on Key Research Project of China (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Friends of Hope Education Fund. Z.C.s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

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Zhou, R., Wang, P., Wong, Y.-C., Xu, H., Lau, S.-Y., Liu, L., Mok, B. W.-Y., Peng, Q., Liu, N., Deng, S., Tam, R. C.-Y., Huang, H., Zhang, A. J., Zhou, D., Zhou, B., Chan, C.-Y., Du, Z., Yang, D., Au, K.-K., Yuen, K.-Y., Chen, H., Chen, Z.. 2021-10-22. Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination. https://doi.org/10.1101/2021.10.21.465252

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