1区 · 综合性期刊
Article
作者: Cooper, Andrew J. R. ; Weinberg, Rona S. ; Hu, Zhe ; Yang, Eun Sung ; Dacon, Cherrelle ; Yewdell, Jonathan W. ; Wang, Lingshu ; Davidson, Edgar ; Lee, Chang-Chun D. ; Nemazee, David ; Leung, Kwanyee ; Crompton, Peter D. ; Chen, Man ; Geraghty, Daniel E. ; Williams, Jazmean K. ; Cong, Yu ; Douagi, Iyadh ; Peterson, Mary ; Tan, Joshua ; Dixit, Saurabh ; Zhang, Yi ; Purser, Lauren ; Moir, Susan ; Byrum, Russell ; Pyo, Chul-Woo ; Mohan, Divya ; Lembirik, Sanae ; Schmaljohn, Connie ; Zhao, Ming ; Tucker, Courtney ; Peng, Linghang ; Yuan, Meng ; Skinner, Jeff ; Mascola, John R. ; Drawbaugh, David ; Holbrook, Michael R. ; Lin, Ting-Hui ; Kollins, Erin ; Perry, Donna ; Eaton, Brett ; Kosik, Ivan ; Pegu, Amarendra ; Wilson, Ian A. ; Huzella, Louis
The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2′ cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain–specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2′ cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.