Neutralizing antibodies to SARS-CoV-2 selected from a human antibody library constructed decades ago

Journal article

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.

Authors: Qiang, M; Ma, P; Li, Y; Liu, H; Harding, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Advanced Science
• Volume: 9
• Issue: 1
• Article number: 2102181
• Place of publication: Germany
• Publication date: 2021-10-29
• Acceptance date: 2021-08-25
• DOI: 10.1002/advs.202102181
• EISSN: 2198-3844
• ISSN: 2198-3844
• Language: English
• Keywords: neutralizing antibody; somatic hypermutation; antibody-antigen interaction; combinatorial antibody library; SARS-CoV-2; variants of concern; COVID-19; FFR