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

tetano

Editor, Senior Moderator
Commun Biol


. 2024 Oct 2;7(1):1239.
doi: 10.1038/s42003-024-06951-7. Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages

Melanie R Walker[SUP] 1 [/SUP], Alexander Underwood[SUP] 2 [/SUP], Kasper H Björnsson[SUP] 1 [/SUP], Sai Sundar Rajan Raghavan[SUP] 1 3 [/SUP], Maria R Bassi[SUP] 1 [/SUP], Alekxander Binderup[SUP] 2 [/SUP], Long V Pham[SUP] 2 [/SUP], Santseharay Ramirez[SUP] 2 [/SUP], Mette Pinholt[SUP] 4 [/SUP], Robert Dagil[SUP] 1 [/SUP], Anne S Knudsen[SUP] 1 [/SUP], Manja Idorn[SUP] 5 [/SUP], Max Soegaard[SUP] 6 [/SUP], Kaituo Wang[SUP] 7 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Ali Salanti[SUP] 1 [/SUP], Jens Bukh[SUP] 2 [/SUP], Lea Barfod[SUP] 8 [/SUP]



Affiliations
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.


 
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