Delineating the functional activity of antibodies with cross-reactivity to SARS-CoV-2, SARS-CoV-1 and related sarbecoviruses

• DOI: 10.1371/journal.ppat.1012650
• Publication Date: 2024-10-28T17:44:40Z
• Authors: Felicitas Ruiz; William B. Foreman; Michelle Lilly; Viren A. Baharani; Delphine M. Depie...; Vrasha Chohan; Ashley L. Taylor; Jamie Guenthoer; Duncan Ralph; Frederick A. Mats...; Helen Y. Chu; Paul D. Bieniasz; Marceline Côté; Tyler N. Starr; Julie Overbaugh
• Keywords: Cross-reactivity

The recurring spillover of pathogenic coronaviruses and demonstrated capacity sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need better understand immune responses this virus family. For purpose, we characterized functional breadth potency antibodies targeting receptor binding domain (RBD) spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 sarbecoviruses from diverse clades animal origins with potential. One neutralizing antibody, C68.61, showed remarkable neutralization both variants viruses different sarbecovirus clades. which targets a conserved RBD class 5 epitope, did not select for escape or culture nor have predicted among circulating strains, suggesting epitope is functionally constrained. We identified 11 additional SARS-CoV-2/SARS-CoV-1 cross-reactive target more sequence 4 epitopes within show activity subset one antibody every single tested. A these Fc-mediated effector functions as potent impact infection outcome models. Thus, our study regions across may serve therapeutics pandemic preparedness well blueprints design immunogens capable eliciting cross-neutralizing responses.