Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2

Abstract Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein represent good candidates to interfere in the Spike/ACE2 interaction, preventing virus cell entry. Since anti-spike mAbs, used individually, might be unable to block the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Margherita Passariello, Chiara Gentile, Veronica Ferrucci, Emanuele Sasso, Cinzia Vetrei, Giovanna Fusco, Maurizio Viscardi, Sergio Brandi, Pellegrino Cerino, Nicola Zambrano, Massimo Zollo, Claudia De Lorenzo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/522ae82dbfd144feacef1182f8f3bee9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:522ae82dbfd144feacef1182f8f3bee9
record_format	dspace
spelling	oai:doaj.org-article:522ae82dbfd144feacef1182f8f3bee92021-12-02T16:53:01ZNovel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-210.1038/s41598-021-90348-72045-2322https://doaj.org/article/522ae82dbfd144feacef1182f8f3bee92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90348-7https://doaj.org/toc/2045-2322Abstract Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein represent good candidates to interfere in the Spike/ACE2 interaction, preventing virus cell entry. Since anti-spike mAbs, used individually, might be unable to block the virus entry in the case of resistant mutations, we designed an innovative strategy for the isolation of multiple novel human scFvs specific for the binding domain (RBD) of Spike. By panning a large phage display antibody library on immobilized RBD, we obtained specific binders by eluting with ACE2 in order to identify those scFvs recognizing the epitope of Spike interacting with its receptor. We converted the novel scFvs into full size IgG4, differently from the previously isolated IgG1 mAbs, to avoid unwanted potential side effects of IgG1 potent effector functions on immune system. The novel antibodies specifically bind to RBD in a nanomolar range and interfere in the interaction of Spike with ACE2 receptor, either used as purified protein or when expressed on cells in its native conformation. Furthermore, some of them have neutralizing activity for virus infection in cell cultures by using two different SARS-CoV-2 isolates including the highly contagious VOC 202012/01 variant and could become useful therapeutic tools to fight against the SARS-CoV-2 virus.Margherita PassarielloChiara GentileVeronica FerrucciEmanuele SassoCinzia VetreiGiovanna FuscoMaurizio ViscardiSergio BrandiPellegrino CerinoNicola ZambranoMassimo ZolloClaudia De LorenzoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Margherita Passariello Chiara Gentile Veronica Ferrucci Emanuele Sasso Cinzia Vetrei Giovanna Fusco Maurizio Viscardi Sergio Brandi Pellegrino Cerino Nicola Zambrano Massimo Zollo Claudia De Lorenzo Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
description	Abstract Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein represent good candidates to interfere in the Spike/ACE2 interaction, preventing virus cell entry. Since anti-spike mAbs, used individually, might be unable to block the virus entry in the case of resistant mutations, we designed an innovative strategy for the isolation of multiple novel human scFvs specific for the binding domain (RBD) of Spike. By panning a large phage display antibody library on immobilized RBD, we obtained specific binders by eluting with ACE2 in order to identify those scFvs recognizing the epitope of Spike interacting with its receptor. We converted the novel scFvs into full size IgG4, differently from the previously isolated IgG1 mAbs, to avoid unwanted potential side effects of IgG1 potent effector functions on immune system. The novel antibodies specifically bind to RBD in a nanomolar range and interfere in the interaction of Spike with ACE2 receptor, either used as purified protein or when expressed on cells in its native conformation. Furthermore, some of them have neutralizing activity for virus infection in cell cultures by using two different SARS-CoV-2 isolates including the highly contagious VOC 202012/01 variant and could become useful therapeutic tools to fight against the SARS-CoV-2 virus.
format	article
author	Margherita Passariello Chiara Gentile Veronica Ferrucci Emanuele Sasso Cinzia Vetrei Giovanna Fusco Maurizio Viscardi Sergio Brandi Pellegrino Cerino Nicola Zambrano Massimo Zollo Claudia De Lorenzo
author_facet	Margherita Passariello Chiara Gentile Veronica Ferrucci Emanuele Sasso Cinzia Vetrei Giovanna Fusco Maurizio Viscardi Sergio Brandi Pellegrino Cerino Nicola Zambrano Massimo Zollo Claudia De Lorenzo
author_sort	Margherita Passariello
title	Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
title_short	Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
title_full	Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
title_fullStr	Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
title_full_unstemmed	Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
title_sort	novel human neutralizing mabs specific for spike-rbd of sars-cov-2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/522ae82dbfd144feacef1182f8f3bee9
work_keys_str_mv	AT margheritapassariello novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT chiaragentile novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT veronicaferrucci novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT emanuelesasso novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT cinziavetrei novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT giovannafusco novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT maurizioviscardi novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT sergiobrandi novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT pellegrinocerino novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT nicolazambrano novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT massimozollo novelhumanneutralizingmabsspecificforspikerbdofsarscov2 AT claudiadelorenzo novelhumanneutralizingmabsspecificforspikerbdofsarscov2
_version_	1718382856505393152

Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2

Ejemplares similares