Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms

SARS-CoV causes an acute infection making targeted passive immunotherapy all attractive treatment strategy. We previously generated human mAbs specific to the SI 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 vital 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 vital 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. (C) 2009 Elsevier Inc. All rights reserved.