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Multi-Clonal Live SARS-CoV-2 In Vitro Neutralization by Antibodies Isolated from Severe COVID-19 Convalescent Donors.
Mor, Michael; Werbner, Michal; Alter, Joel; Safra, Modi; Chomsky, Elad; Hada-Neeman, Smadar; Polonsky, Ksenia; Nowell, Cameron J; Clark, Alex E; Roitburd-Berman, Anna; Shalom, Noam Ben; Navon, Michal; Rafael, Dor; Sharim, Hila; Kiner, Evgeny; Griffis, Eric; Gershoni, Jonathan M; Kobiler, Oren; Leibel, Sandra Lawrynowicz; Zimhony, Oren; Carlin, Aaron F; Yaari, Gur; Dassau, Moshe; Gal-Tanamy, Meital; Hagin, David; Croker, Ben A; Freund, Natalia T.
Afiliación
  • Mor M; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
  • Werbner M; Azrieli Faculty of Medicine, Bar Ilan University, 2800123, Israel.
  • Alter J; Azrieli Faculty of Medicine, Bar Ilan University, 2800123, Israel.
  • Safra M; Faculty of Engineering, Bar Ilan University, 5290002, Israel.
  • Chomsky E; ImmunAi, USA.
  • Hada-Neeman S; George S Weiss, Life sciences Faculty, Tel Aviv University, 699780, Israel.
  • Polonsky K; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
  • Nowell CJ; Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia.
  • Clark AE; Department of Cellular and Molecular Medicine, School of Medicine, UC San Diego, La Jolla, CA 92093 USA.
  • Roitburd-Berman A; George S Weiss, Life sciences Faculty, Tel Aviv University, 699780, Israel.
  • Shalom NB; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
  • Navon M; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
  • Rafael D; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
  • Sharim H; ImmunAi, USA.
  • Kiner E; ImmunAi, USA.
  • Griffis E; Nikon Imaging Center, UC San Diego, CA, 92093 USA.
  • Gershoni JM; George S Weiss, Life sciences Faculty, Tel Aviv University, 699780, Israel.
  • Kobiler O; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
  • Leibel SL; Department of Pediatrics, School of Medicine, UC San Diego, La Jolla, CA 92093 USA.
  • Zimhony O; Infectious Diseases unit, Kaplan Medical Center, Rehovot, 7610001, affiliated to the School of Medicine Hebrew University and Hadassah, Israel.
  • Carlin AF; Department of Cellular and Molecular Medicine, School of Medicine, UC San Diego, La Jolla, CA 92093 USA.
  • Yaari G; Faculty of Engineering, Bar Ilan University, 5290002, Israel.
  • Dassau M; Azrieli Faculty of Medicine, Bar Ilan University, 2800123, Israel.
  • Gal-Tanamy M; Azrieli Faculty of Medicine, Bar Ilan University, 2800123, Israel.
  • Hagin D; Department of Immunology Ichilov Hospital, 623906, Israel.
  • Croker BA; Department of Pediatrics, School of Medicine, UC San Diego, La Jolla, CA 92093 USA.
  • Freund NT; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Israel.
bioRxiv ; 2020 Oct 06.
Article en En | MEDLINE | ID: mdl-33052341
The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe and not mild infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of viral inhibition. B cell receptor (BCR) sequencing revealed two VH genes, VH3-38 and VH3-53, that were enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against live SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and RBD mutagenesis, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2020 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2020 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos