Broadly neutralizing antibodies target the coronavirus fusion peptide.

Abstract

The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.

One-Sentence Summary:

Rare monoclonal antibodies from COVID-19 convalescent individuals broadly neutralize coronaviruses by targeting the fusion peptide.

• Authors: Cherrelle Dacon, Courtney Tucker, Linghang Peng, Chang-Chun D Lee, Ting-Hui Lin, Meng Yuan, Yu Cong, Lingshu Wang, Lauren Purser, Jazmean K Williams, Chul-Woo Pyo, Ivan Kosik, Zhe Hu, Ming Zhao, Divya Mohan, Andrew Cooper, Mary Peterson, Jeff Skinner, Saurabh Dixit, Erin Kollins, Louis Huzella, Donna Perry, Russell Byrum, Sanae Lembirik, Yi Zhang, Eun Sung Yang, Man Chen, Kwanyee Leung, Rona S Weinberg, Amarendra Pegu, Daniel E Geraghty, Edgar Davidson, Iyadh Douagi, Susan Moir, Jonathan W Yewdell, Connie Schmaljohn, Peter D Crompton, Michael R Holbrook, David Nemazee, John R Mascola, Ian A Wilson, Joshua Tan
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Apr 12 2022) United States
• PMID: 35441178 (Publication Type: Preprint)