Comprehensive Evaluation of ACE2-Fc Combination with Neutralization Antibody on Broad Protection against SARS-CoV-2 and Its Variants
Tang, H.; Ke, Y.; Ma, H.; Han, L.; Wang, L.; Zong, H.; Yuan, Y.; Wang, Z.; He, Y.; Chang, Y.; Wang, S.; Liu, J.; Yue, Y.; Xu, W.; Zhang, X.; Wang, Z.; Yang, L.; Chen, H.; Bian, Y.; Zhang, B.; Liao, Y.; Yin, H.; Chen, Y.; Zhang, E.; Zhang, X.; Jiang, H.; Xie, Y.; Gilly, J.; Wu, M.; Sun, T.; Zhu, J.
Show abstract
Emerging SARS-CoV-2 variants are threatening the efficacy of antibody therapies. Combination treatments including ACE2-Fc have been developed to overcome the evasion of neutralizing antibodies (NAbs) in individual cases. Here we conducted a comprehensive evaluation of this strategy by combining ACE2-Fc with NAbs of diverse epitopes on the RBD. NAb+ACE2-Fc combinations efficiently neutralized HIV-based pseudovirus carrying the spike protein of the Delta or Omicron variants, achieving a balance between efficacy and breadth. In an antibody escape assay using replication-competent VSV-SARS-CoV-2-S, all the combinations had no escape after fifteen passages. By comparison, all the NAbs without combo with ACE2-Fc had escaped within six passages. Further, the VSV-S variants escaped from NAbs were neutralized by ACE2-Fc, revealing the mechanism of NAb+ACE2-Fc combinations survived after fifteen passages. We finally examined ACE2-Fc neutralization against pseudovirus variants that were resistant to the therapeutic antibodies currently in clinic. Our results suggest ACE2-Fc is a universal combination partner to combat SARS-CoV-2 variants including Delta and Omicron.
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