Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 2021-02, Vol.371 (6531), p.823-829
Hauptverfasser: Rappazzo, C Garrett, Tse, Longping V, Kaku, Chengzi I, Wrapp, Daniel, Sakharkar, Mrunal, Huang, Deli, Deveau, Laura M, Yockachonis, Thomas J, Herbert, Andrew S, Battles, Michael B, O'Brien, Cecilia M, Brown, Michael E, Geoghegan, James C, Belk, Jonathan, Peng, Linghang, Yang, Linlin, Hou, Yixuan, Scobey, Trevor D, Burton, Dennis R, Nemazee, David, Dye, John M, Voss, James E, Gunn, Bronwyn M, McLellan, Jason S, Baric, Ralph S, Gralinski, Lisa E, Walker, Laura M
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Sprache:eng
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Zusammenfassung:The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (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 and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration 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 against clade 1 sarbecoviruses.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abf4830