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  • An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.

An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.

bioRxiv : the preprint server for biology (2020-11-26)
C Garrett Rappazzo, Longping V Tse, Chengzi I Kaku, Daniel Wrapp, Mrunal Sakharkar, Deli Huang, Laura M Deveau, Thomas J Yockachonis, Andrew S Herbert, Michael B Battles, Cecilia M O'Brien, Michael E Brown, James C Geoghegan, Jonathan Belk, Linghang Peng, Linlin Yang, Trevor D Scobey, Dennis R Burton, David Nemazee, John M Dye, James E Voss, Bronwyn M Gunn, Jason S McLellan, Ralph S Baric, Lisa E Gralinski, Laura M Walker
PMID33236009
ABSTRACT

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs.