Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages.

Autor: Walker MR; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Underwood A; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Björnsson KH; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Raghavan SSR; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Bassi MR; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Binderup A; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Pham LV; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ramirez S; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Pinholt M; Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Denmark., Dagil R; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Knudsen AS; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Idorn M; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Soegaard M; ExpreS2ion Biotechnologies, Hørsholm, Denmark., Wang K; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Salanti A; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Bukh J; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Barfod L; Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. lbarfod@sund.ku.dk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Oct 02; Vol. 7 (1), pp. 1239. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1038/s42003-024-06951-7
Abstrakt: The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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