Science (New York, N.Y.) · 2021
Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.
Предметные рубрики MeSH
Angiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, ViralAntibody AffinityBetacoronavirusBinding SitesBinding Sites, AntibodyBroadly Neutralizing AntibodiesCOVID-19Cell Surface Display TechniquesDirected Molecular EvolutionEpitopesHumansImmunization, PassiveImmunoglobulin Fc FragmentsMice, Inbred BALB CProtein DomainsProtein EngineeringReceptors, CoronavirusSevere acute respiratory syndrome-related coronavirusSARS-CoV-2Severe Acute Respiratory SyndromeSpike Glycoprotein, CoronavirusCOVID-19 SerotherapyMice