Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Li, T.; Han, X.; Gu, C.; Guo, H.; Zhang, H.; Wang, Y.; Hu, C.; Wang, K.; Liu, F.; Luo, F.; Zhang, Y.; Hu, J.; wang, W.; Li, S.; Hao, Y.; Shen, M.; Huang, J.; Long, Y.; Song, S.; Wu, R.; Mu, S.; Chen, Q.; Gao, F.; Wang, J.; Long, S.; Li, L.; Wu, Y.; Gao, Y.; Xu, W.; Cai, X.; Qu, D.; Zhang, Z.; Li, N.; Gao, Q.; Zhang, g.; He, C.; Wang, W.; Ji, X.; Tang, N.; Yuan, Z.; Xie, Y.; Zhang, B.; Yang, H.; Huang, A.; Jin, A.

doi:10.1101/2021.04.19.440481

bioRxiv · 10.1101/2021.04.19.440481

Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Li, T.·Han, X.·Gu, C.·Guo, H.·Zhang, H.·Wang, Y.·Hu, C.·Wang, K.·Liu, F.·Luo, F.·Zhang, Y.·Hu, J.·wang, W.·Li, S.·Hao, Y.·Shen, M.·Huang, J.·Long, Y.·Song, S.·Wu, R.·Mu, S.·Chen, Q.·Gao, F.·Wang, J.·Long, S.·Li, L.·Wu, Y.·Gao, Y.·Xu, W.·Cai, X.·Qu, D.·Zhang, Z.·Li, N.·Gao, Q.·Zhang, g.·He, C.·Wang, W.·Ji, X.·Tang, N.·Yuan, Z.·Xie, Y.·Zhang, B.·Yang, H.·Huang, A.·Jin, A.

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Abstract

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.

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Li, T., Han, X., Gu, C., Guo, H., Zhang, H., Wang, Y., Hu, C., Wang, K., Liu, F., Luo, F., Zhang, Y., Hu, J., wang, W., Li, S., Hao, Y., Shen, M., Huang, J., Long, Y., Song, S., Wu, R., Mu, S., Chen, Q., Gao, F., Wang, J., Long, S., Li, L., Wu, Y., Gao, Y., Xu, W., Cai, X., Qu, D., Zhang, Z., Li, N., Gao, Q., Zhang, g., He, C., Wang, W., Ji, X., Tang, N., Yuan, Z., Xie, Y., Zhang, B., Yang, H., Huang, A., Jin, A.. 2021-04-20. Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants. https://doi.org/10.1101/2021.04.19.440481

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