tetano
Editor, Senior Moderator
Cell Host Microbe
. 2022 Nov 4;S1931-3128(22)00523-6.
doi: 10.1016/j.chom.2022.10.010. Online ahead of print.
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses
Cherrelle Dacon[SUP] 1 [/SUP], Linghang Peng[SUP] 2 [/SUP], Ting-Hui Lin[SUP] 3 [/SUP], Courtney Tucker[SUP] 4 [/SUP], Chang-Chun D Lee[SUP] 3 [/SUP], Yu Cong[SUP] 5 [/SUP], Lingshu Wang[SUP] 6 [/SUP], Lauren Purser[SUP] 1 [/SUP], Andrew J R Cooper[SUP] 1 [/SUP], Jazmean K Williams[SUP] 7 [/SUP], Chul-Woo Pyo[SUP] 8 [/SUP], Meng Yuan[SUP] 3 [/SUP], Ivan Kosik[SUP] 9 [/SUP], Zhe Hu[SUP] 9 [/SUP], Ming Zhao[SUP] 10 [/SUP], Divya Mohan[SUP] 1 [/SUP], Mary Peterson[SUP] 11 [/SUP], Jeff Skinner[SUP] 11 [/SUP], Saurabh Dixit[SUP] 5 [/SUP], Erin Kollins[SUP] 5 [/SUP], Louis Huzella[SUP] 5 [/SUP], Donna Perry[SUP] 5 [/SUP], Russell Byrum[SUP] 5 [/SUP], Sanae Lembirik[SUP] 5 [/SUP], Michael Murphy[SUP] 5 [/SUP], Yi Zhang[SUP] 6 [/SUP], Eun Sung Yang[SUP] 6 [/SUP], Man Chen[SUP] 6 [/SUP], Kwanyee Leung[SUP] 6 [/SUP], Rona S Weinberg[SUP] 12 [/SUP], Amarendra Pegu[SUP] 6 [/SUP], Daniel E Geraghty[SUP] 8 [/SUP], Edgar Davidson[SUP] 7 [/SUP], Benjamin J Doranz[SUP] 7 [/SUP], Iyadh Douagi[SUP] 13 [/SUP], Susan Moir[SUP] 14 [/SUP], Jonathan W Yewdell[SUP] 9 [/SUP], Connie Schmaljohn[SUP] 5 [/SUP], Peter D Crompton[SUP] 11 [/SUP], John R Mascola[SUP] 6 [/SUP], Michael R Holbrook[SUP] 5 [/SUP], David Nemazee[SUP] 2 [/SUP], Ian A Wilson[SUP] 15 [/SUP], Joshua Tan[SUP] 16 [/SUP]
Affiliations
Abstract
Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; betacoronavirus; broadly neutralizing antibodies; monoclonal antibody; stem helix; variants of concern.
. 2022 Nov 4;S1931-3128(22)00523-6.
doi: 10.1016/j.chom.2022.10.010. Online ahead of print.
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses
Cherrelle Dacon[SUP] 1 [/SUP], Linghang Peng[SUP] 2 [/SUP], Ting-Hui Lin[SUP] 3 [/SUP], Courtney Tucker[SUP] 4 [/SUP], Chang-Chun D Lee[SUP] 3 [/SUP], Yu Cong[SUP] 5 [/SUP], Lingshu Wang[SUP] 6 [/SUP], Lauren Purser[SUP] 1 [/SUP], Andrew J R Cooper[SUP] 1 [/SUP], Jazmean K Williams[SUP] 7 [/SUP], Chul-Woo Pyo[SUP] 8 [/SUP], Meng Yuan[SUP] 3 [/SUP], Ivan Kosik[SUP] 9 [/SUP], Zhe Hu[SUP] 9 [/SUP], Ming Zhao[SUP] 10 [/SUP], Divya Mohan[SUP] 1 [/SUP], Mary Peterson[SUP] 11 [/SUP], Jeff Skinner[SUP] 11 [/SUP], Saurabh Dixit[SUP] 5 [/SUP], Erin Kollins[SUP] 5 [/SUP], Louis Huzella[SUP] 5 [/SUP], Donna Perry[SUP] 5 [/SUP], Russell Byrum[SUP] 5 [/SUP], Sanae Lembirik[SUP] 5 [/SUP], Michael Murphy[SUP] 5 [/SUP], Yi Zhang[SUP] 6 [/SUP], Eun Sung Yang[SUP] 6 [/SUP], Man Chen[SUP] 6 [/SUP], Kwanyee Leung[SUP] 6 [/SUP], Rona S Weinberg[SUP] 12 [/SUP], Amarendra Pegu[SUP] 6 [/SUP], Daniel E Geraghty[SUP] 8 [/SUP], Edgar Davidson[SUP] 7 [/SUP], Benjamin J Doranz[SUP] 7 [/SUP], Iyadh Douagi[SUP] 13 [/SUP], Susan Moir[SUP] 14 [/SUP], Jonathan W Yewdell[SUP] 9 [/SUP], Connie Schmaljohn[SUP] 5 [/SUP], Peter D Crompton[SUP] 11 [/SUP], John R Mascola[SUP] 6 [/SUP], Michael R Holbrook[SUP] 5 [/SUP], David Nemazee[SUP] 2 [/SUP], Ian A Wilson[SUP] 15 [/SUP], Joshua Tan[SUP] 16 [/SUP]
Affiliations
- PMID: 36347257
- DOI: 10.1016/j.chom.2022.10.010
Abstract
Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; betacoronavirus; broadly neutralizing antibodies; monoclonal antibody; stem helix; variants of concern.