tetano
Editor, Senior Moderator
Cell Rep
. 2021 Jun 22;109353.
doi: 10.1016/j.celrep.2021.109353. Online ahead of print.
Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
Madeleine F Jennewein[SUP] 1 [/SUP], Anna J MacCamy[SUP] 1 [/SUP], Nicholas R Akins[SUP] 1 [/SUP], Junli Feng[SUP] 1 [/SUP], Leah J Homad[SUP] 1 [/SUP], Nicholas K Hurlburt[SUP] 1 [/SUP], Emilie Seydoux[SUP] 1 [/SUP], Yu-Hsin Wan[SUP] 1 [/SUP], Andrew B Stuart[SUP] 1 [/SUP], Venkata Viswanadh Edara[SUP] 2 [/SUP], Katharine Floyd[SUP] 2 [/SUP], Abigail Vanderheiden[SUP] 2 [/SUP], John R Mascola[SUP] 3 [/SUP], Nicole Doria-Rose[SUP] 3 [/SUP], Lingshu Wang[SUP] 3 [/SUP], Eun Sung Yang[SUP] 3 [/SUP], Helen Y Chu[SUP] 4 [/SUP], Jonathan L Torres[SUP] 5 [/SUP], Gabriel Ozorowski[SUP] 5 [/SUP], Andrew B Ward[SUP] 5 [/SUP], Rachael E Whaley[SUP] 1 [/SUP], Kristen W Cohen[SUP] 1 [/SUP], Marie Pancera[SUP] 6 [/SUP], M Juliana McElrath[SUP] 7 [/SUP], Janet A Englund[SUP] 8 [/SUP], Andrés Finzi[SUP] 9 [/SUP], Mehul S Suthar[SUP] 10 [/SUP], Andrew T McGuire[SUP] 11 [/SUP], Leonidas Stamatatos[SUP] 12 [/SUP]
Affiliations
Abstract
SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
Keywords: B.1.351; CV3-25; NTD; RBD; S2 subunit; SARS-CoV-1; SARS-CoV-2; monoclonal antibodies; neutralization.
. 2021 Jun 22;109353.
doi: 10.1016/j.celrep.2021.109353. Online ahead of print.
Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
Madeleine F Jennewein[SUP] 1 [/SUP], Anna J MacCamy[SUP] 1 [/SUP], Nicholas R Akins[SUP] 1 [/SUP], Junli Feng[SUP] 1 [/SUP], Leah J Homad[SUP] 1 [/SUP], Nicholas K Hurlburt[SUP] 1 [/SUP], Emilie Seydoux[SUP] 1 [/SUP], Yu-Hsin Wan[SUP] 1 [/SUP], Andrew B Stuart[SUP] 1 [/SUP], Venkata Viswanadh Edara[SUP] 2 [/SUP], Katharine Floyd[SUP] 2 [/SUP], Abigail Vanderheiden[SUP] 2 [/SUP], John R Mascola[SUP] 3 [/SUP], Nicole Doria-Rose[SUP] 3 [/SUP], Lingshu Wang[SUP] 3 [/SUP], Eun Sung Yang[SUP] 3 [/SUP], Helen Y Chu[SUP] 4 [/SUP], Jonathan L Torres[SUP] 5 [/SUP], Gabriel Ozorowski[SUP] 5 [/SUP], Andrew B Ward[SUP] 5 [/SUP], Rachael E Whaley[SUP] 1 [/SUP], Kristen W Cohen[SUP] 1 [/SUP], Marie Pancera[SUP] 6 [/SUP], M Juliana McElrath[SUP] 7 [/SUP], Janet A Englund[SUP] 8 [/SUP], Andrés Finzi[SUP] 9 [/SUP], Mehul S Suthar[SUP] 10 [/SUP], Andrew T McGuire[SUP] 11 [/SUP], Leonidas Stamatatos[SUP] 12 [/SUP]
Affiliations
- PMID: 34237283
- PMCID: PMC8216847
- DOI: 10.1016/j.celrep.2021.109353
Abstract
SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
Keywords: B.1.351; CV3-25; NTD; RBD; S2 subunit; SARS-CoV-1; SARS-CoV-2; monoclonal antibodies; neutralization.