Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine

Lu, C.; Zhang, Y.; Liu, X.; Hou, F.; Cai, R.; Yu, Z.; Liu, F.; Yang, G.; Ding, J.; Xu, J.; Hua, X.; Pan, X.; Liu, L.; Lin, K.; Wang, Z.; Li, X.; Lu, J.; Zhang, Q.; Li, Y.; Hu, C.; Fan, H.; Wang, H.; Jia, R.; Xu, F.; Wang, X.; Huang, H.; Zhao, R.; Li, J.; Cheng, H.; Jia, W.; Yang, X.

doi:10.1101/2022.09.06.506714

bioRxiv · 10.1101/2022.09.06.506714

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine

Lu, C.·Zhang, Y.·Liu, X.·Hou, F.·Cai, R.·Yu, Z.·Liu, F.·Yang, G.·Ding, J.·Xu, J.·Hua, X.·Pan, X.·Liu, L.·Lin, K.·Wang, Z.·Li, X.·Lu, J.·Zhang, Q.·Li, Y.·Hu, C.·Fan, H.·Wang, H.·Jia, R.·Xu, F.·Wang, X.·Huang, H.·Zhao, R.·Li, J.·Cheng, H.·Jia, W.·Yang, X.

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Abstract

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants following an order of BA.1>BA.2>BA.4/5. In naive animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccines targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection across all VOCs. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine- primed populations.

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Lu, C., Zhang, Y., Liu, X., Hou, F., Cai, R., Yu, Z., Liu, F., Yang, G., Ding, J., Xu, J., Hua, X., Pan, X., Liu, L., Lin, K., Wang, Z., Li, X., Lu, J., Zhang, Q., Li, Y., Hu, C., Fan, H., Wang, H., Jia, R., Xu, F., Wang, X., Huang, H., Zhao, R., Li, J., Cheng, H., Jia, W., Yang, X.. 2022-09-06. Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine. https://doi.org/10.1101/2022.09.06.506714

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