tetano
Editor, Senior Moderator
Science
. 2022 Jul 12;eabq3773.
doi: 10.1126/science.abq3773. Online ahead of print.
Broadly neutralizing antibodies target the coronavirus fusion peptide
Cherrelle Dacon[SUP] #[/SUP][SUP] 1 [/SUP], Courtney Tucker[SUP] #[/SUP][SUP] 1 [/SUP], Linghang Peng[SUP] #[/SUP][SUP] 2 [/SUP], Chang-Chun D Lee[SUP] #[/SUP][SUP] 3 [/SUP], Ting-Hui Lin[SUP] 3 [/SUP], Meng Yuan[SUP] 3 [/SUP], Yu Cong[SUP] 4 [/SUP], Lingshu Wang[SUP] 5 [/SUP], Lauren Purser[SUP] 1 [/SUP], Jazmean K Williams[SUP] 6 [/SUP], Chul-Woo Pyo[SUP] 7 [/SUP], Ivan Kosik[SUP] 8 [/SUP], Zhe Hu[SUP] 8 [/SUP], Ming Zhao[SUP] 9 [/SUP], Divya Mohan[SUP] 1 [/SUP], Andrew J R Cooper[SUP] 1 [/SUP], Mary Peterson[SUP] 10 [/SUP], Jeff Skinner[SUP] 10 [/SUP], Saurabh Dixit[SUP] 4 [/SUP], Erin Kollins[SUP] 4 [/SUP], Louis Huzella[SUP] 4 [/SUP], Donna Perry[SUP] 4 [/SUP], Russell Byrum[SUP] 4 [/SUP], Sanae Lembirik[SUP] 4 [/SUP], David Drawbaugh[SUP] 4 [/SUP], Brett Eaton[SUP] 4 [/SUP], Yi Zhang[SUP] 5 [/SUP], Eun Sung Yang[SUP] 5 [/SUP], Man Chen[SUP] 5 [/SUP], Kwanyee Leung[SUP] 5 [/SUP], Rona S Weinberg[SUP] 11 [/SUP], Amarendra Pegu[SUP] 5 [/SUP], Daniel E Geraghty[SUP] 7 [/SUP], Edgar Davidson[SUP] 6 [/SUP], Iyadh Douagi[SUP] 12 [/SUP], Susan Moir[SUP] 13 [/SUP], Jonathan W Yewdell[SUP] 8 [/SUP], Connie Schmaljohn[SUP] 4 [/SUP], Peter D Crompton[SUP] 10 [/SUP], Michael R Holbrook[SUP] 4 [/SUP], David Nemazee[SUP] 2 [/SUP], John R Mascola[SUP] 5 [/SUP], Ian A Wilson[SUP] 3 14 [/SUP], Joshua Tan[SUP] 1 [/SUP]
Affiliations
Abstract
The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We use 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 beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.2 and BA.4/5, 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. 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.
. 2022 Jul 12;eabq3773.
doi: 10.1126/science.abq3773. Online ahead of print.
Broadly neutralizing antibodies target the coronavirus fusion peptide
Cherrelle Dacon[SUP] #[/SUP][SUP] 1 [/SUP], Courtney Tucker[SUP] #[/SUP][SUP] 1 [/SUP], Linghang Peng[SUP] #[/SUP][SUP] 2 [/SUP], Chang-Chun D Lee[SUP] #[/SUP][SUP] 3 [/SUP], Ting-Hui Lin[SUP] 3 [/SUP], Meng Yuan[SUP] 3 [/SUP], Yu Cong[SUP] 4 [/SUP], Lingshu Wang[SUP] 5 [/SUP], Lauren Purser[SUP] 1 [/SUP], Jazmean K Williams[SUP] 6 [/SUP], Chul-Woo Pyo[SUP] 7 [/SUP], Ivan Kosik[SUP] 8 [/SUP], Zhe Hu[SUP] 8 [/SUP], Ming Zhao[SUP] 9 [/SUP], Divya Mohan[SUP] 1 [/SUP], Andrew J R Cooper[SUP] 1 [/SUP], Mary Peterson[SUP] 10 [/SUP], Jeff Skinner[SUP] 10 [/SUP], Saurabh Dixit[SUP] 4 [/SUP], Erin Kollins[SUP] 4 [/SUP], Louis Huzella[SUP] 4 [/SUP], Donna Perry[SUP] 4 [/SUP], Russell Byrum[SUP] 4 [/SUP], Sanae Lembirik[SUP] 4 [/SUP], David Drawbaugh[SUP] 4 [/SUP], Brett Eaton[SUP] 4 [/SUP], Yi Zhang[SUP] 5 [/SUP], Eun Sung Yang[SUP] 5 [/SUP], Man Chen[SUP] 5 [/SUP], Kwanyee Leung[SUP] 5 [/SUP], Rona S Weinberg[SUP] 11 [/SUP], Amarendra Pegu[SUP] 5 [/SUP], Daniel E Geraghty[SUP] 7 [/SUP], Edgar Davidson[SUP] 6 [/SUP], Iyadh Douagi[SUP] 12 [/SUP], Susan Moir[SUP] 13 [/SUP], Jonathan W Yewdell[SUP] 8 [/SUP], Connie Schmaljohn[SUP] 4 [/SUP], Peter D Crompton[SUP] 10 [/SUP], Michael R Holbrook[SUP] 4 [/SUP], David Nemazee[SUP] 2 [/SUP], John R Mascola[SUP] 5 [/SUP], Ian A Wilson[SUP] 3 14 [/SUP], Joshua Tan[SUP] 1 [/SUP]
Affiliations
- PMID: 35857439
- DOI: 10.1126/science.abq3773
Abstract
The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We use 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 beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.2 and BA.4/5, 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. 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.