tetano
Editor, Senior Moderator
Cell Rep
. 2021 Sep 16;109784.
doi: 10.1016/j.celrep.2021.109784. Online ahead of print.
Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition
Kevin J Kramer[SUP] 1 [/SUP], Nicole V Johnson[SUP] 2 [/SUP], Andrea R Shiakolas[SUP] 1 [/SUP], Naveenchandra Suryadevara[SUP] 3 [/SUP], Sivakumar Periasamy[SUP] 4 [/SUP], Nagarajan Raju[SUP] 3 [/SUP], Jazmean K Williams[SUP] 5 [/SUP], Daniel Wrapp[SUP] 2 [/SUP], Seth J Zost[SUP] 3 [/SUP], Lauren M Walker[SUP] 1 [/SUP], Steven C Wall[SUP] 1 [/SUP], Clinton M Holt[SUP] 6 [/SUP], Ching-Lin Hsieh[SUP] 2 [/SUP], Rachel E Sutton[SUP] 3 [/SUP], Ariana Paulo[SUP] 3 [/SUP], Rachel S Nargi[SUP] 3 [/SUP], Edgar Davidson[SUP] 5 [/SUP], Benjamin J Doranz[SUP] 5 [/SUP], James E Crowe Jr[SUP] 7 [/SUP], Alexander Bukreyev[SUP] 4 [/SUP], Robert H Carnahan[SUP] 8 [/SUP], Jason S McLellan[SUP] 9 [/SUP], Ivelin S Georgiev[SUP] 10 [/SUP]
Affiliations
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.
Keywords: COVID-19; Delta variant; LIBRA-seq; SARS-CoV-2; antibody discovery; cryo-EM; monoclonal antibodies biology.
. 2021 Sep 16;109784.
doi: 10.1016/j.celrep.2021.109784. Online ahead of print.
Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition
Kevin J Kramer[SUP] 1 [/SUP], Nicole V Johnson[SUP] 2 [/SUP], Andrea R Shiakolas[SUP] 1 [/SUP], Naveenchandra Suryadevara[SUP] 3 [/SUP], Sivakumar Periasamy[SUP] 4 [/SUP], Nagarajan Raju[SUP] 3 [/SUP], Jazmean K Williams[SUP] 5 [/SUP], Daniel Wrapp[SUP] 2 [/SUP], Seth J Zost[SUP] 3 [/SUP], Lauren M Walker[SUP] 1 [/SUP], Steven C Wall[SUP] 1 [/SUP], Clinton M Holt[SUP] 6 [/SUP], Ching-Lin Hsieh[SUP] 2 [/SUP], Rachel E Sutton[SUP] 3 [/SUP], Ariana Paulo[SUP] 3 [/SUP], Rachel S Nargi[SUP] 3 [/SUP], Edgar Davidson[SUP] 5 [/SUP], Benjamin J Doranz[SUP] 5 [/SUP], James E Crowe Jr[SUP] 7 [/SUP], Alexander Bukreyev[SUP] 4 [/SUP], Robert H Carnahan[SUP] 8 [/SUP], Jason S McLellan[SUP] 9 [/SUP], Ivelin S Georgiev[SUP] 10 [/SUP]
Affiliations
- PMID: 34592170
- DOI: 10.1016/j.celrep.2021.109784
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.
Keywords: COVID-19; Delta variant; LIBRA-seq; SARS-CoV-2; antibody discovery; cryo-EM; monoclonal antibodies biology.