title: Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms.
abstract: SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.
authors.affiliation: Department of Microbiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Coughlin
authors.forename: John
authors.initials: J
authors.lastname: Babcook
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D020128:Inhibitory Concentration 50; D009154:Mutation; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000502:physiology*; D014709:Vero Cells; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents