tetano
Editor, Senior Moderator
Adv Sci (Weinh)
. 2021 Oct 29;e2102181.
doi: 10.1002/advs.202102181. Online ahead of print.
Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago
Min Qiang[SUP] 1 [/SUP], Peixiang Ma[SUP] 1 [/SUP], Yu Li[SUP] 1 2 3 4 [/SUP], Hejun Liu[SUP] 5 [/SUP], Adam Harding[SUP] 6 [/SUP], Chenyu Min[SUP] 7 [/SUP], Fulian Wang[SUP] 1 2 3 4 [/SUP], Lili Liu[SUP] 1 [/SUP], Meng Yuan[SUP] 5 [/SUP], Qun Ji[SUP] 1 [/SUP], Pingdong Tao[SUP] 1 2 3 4 [/SUP], Xiaojie Shi[SUP] 1 [/SUP], Zhean Li[SUP] 1 [/SUP], Teng Li[SUP] 1 2 3 4 [/SUP], Xian Wang[SUP] 1 2 3 4 [/SUP], Yu Zhang[SUP] 2 [/SUP], Nicholas C Wu[SUP] 5 [/SUP], Chang-Chun D Lee[SUP] 5 [/SUP], Xueyong Zhu[SUP] 5 [/SUP], Javier Gilbert-Jaramillo[SUP] 6 [/SUP], Chuyue Zhang[SUP] 1 2 3 4 [/SUP], Abhishek Saxena[SUP] 1 [/SUP], Xingxu Huang[SUP] 2 [/SUP], Hou Wang[SUP] 8 [/SUP], William James[SUP] 6 [/SUP], Raymond A Dwek[SUP] 9 [/SUP], Ian A Wilson[SUP] 5 10 [/SUP], Guang Yang[SUP] 1 7 [/SUP], Richard A Lerner[SUP] 11 [/SUP]
Affiliations
Abstract
Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.
Keywords: COVID-19; SARS-CoV-2; antibody-antigen interaction; combinatorial antibody library; neutralizing antibody; somatic hypermutation; variants of concern.
. 2021 Oct 29;e2102181.
doi: 10.1002/advs.202102181. Online ahead of print.
Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago
Min Qiang[SUP] 1 [/SUP], Peixiang Ma[SUP] 1 [/SUP], Yu Li[SUP] 1 2 3 4 [/SUP], Hejun Liu[SUP] 5 [/SUP], Adam Harding[SUP] 6 [/SUP], Chenyu Min[SUP] 7 [/SUP], Fulian Wang[SUP] 1 2 3 4 [/SUP], Lili Liu[SUP] 1 [/SUP], Meng Yuan[SUP] 5 [/SUP], Qun Ji[SUP] 1 [/SUP], Pingdong Tao[SUP] 1 2 3 4 [/SUP], Xiaojie Shi[SUP] 1 [/SUP], Zhean Li[SUP] 1 [/SUP], Teng Li[SUP] 1 2 3 4 [/SUP], Xian Wang[SUP] 1 2 3 4 [/SUP], Yu Zhang[SUP] 2 [/SUP], Nicholas C Wu[SUP] 5 [/SUP], Chang-Chun D Lee[SUP] 5 [/SUP], Xueyong Zhu[SUP] 5 [/SUP], Javier Gilbert-Jaramillo[SUP] 6 [/SUP], Chuyue Zhang[SUP] 1 2 3 4 [/SUP], Abhishek Saxena[SUP] 1 [/SUP], Xingxu Huang[SUP] 2 [/SUP], Hou Wang[SUP] 8 [/SUP], William James[SUP] 6 [/SUP], Raymond A Dwek[SUP] 9 [/SUP], Ian A Wilson[SUP] 5 10 [/SUP], Guang Yang[SUP] 1 7 [/SUP], Richard A Lerner[SUP] 11 [/SUP]
Affiliations
- PMID: 34716683
- DOI: 10.1002/advs.202102181
Abstract
Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.
Keywords: COVID-19; SARS-CoV-2; antibody-antigen interaction; combinatorial antibody library; neutralizing antibody; somatic hypermutation; variants of concern.