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

Autor: Melanie R. Walker, Alexander Underwood, Kasper H. Björnsson, Sai Sundar Rajan Raghavan, Maria R. Bassi, Alekxander Binderup, Long V. Pham, Santseharay Ramirez, Mette Pinholt, Robert Dagil, Anne S. Knudsen, Manja Idorn, Max Soegaard, Kaituo Wang, Andrew B. Ward, Ali Salanti, Jens Bukh, Lea Barfod
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-06951-7
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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