XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants

Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of mult...

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Autores principales:	Bernard Vanhove, Stéphane Marot, Ray T. So, Benjamin Gaborit, Gwénaëlle Evanno, Isabelle Malet, Guillaume Lafrogne, Edwige Mevel, Carine Ciron, Pierre-Joseph Royer, Elsa Lheriteau, François Raffi, Roberto Bruzzone, Chris Ka Pun Mok, Odile Duvaux, Anne-Geneviève Marcelin, Vincent Calvez
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	COVID-19 polyclonal antibody (PAb) SARS-CoV-2 variants neutralization Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6f9f8633566c421f939f2280d4799e1e
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spelling	oai:doaj.org-article:6f9f8633566c421f939f2280d4799e1e2021-11-15T06:23:46ZXAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants1664-322410.3389/fimmu.2021.761250https://doaj.org/article/6f9f8633566c421f939f2280d4799e1e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.761250/fullhttps://doaj.org/toc/1664-3224Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBMs), in direct contact sites with the angiotensin converting enzyme-2 (ACE-2). Therefore, in Spike/ACE-2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study on Vero E6 cells conducted over 1 month, no mutation was associated with the addition of increasing doses of XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE-2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19) including the different variants of concern identified so far.Bernard VanhoveStéphane MarotRay T. SoBenjamin GaboritBenjamin GaboritGwénaëlle EvannoIsabelle MaletGuillaume LafrogneEdwige MevelCarine CironPierre-Joseph RoyerElsa LheriteauFrançois RaffiFrançois RaffiRoberto BruzzoneRoberto BruzzoneChris Ka Pun MokChris Ka Pun MokOdile DuvauxAnne-Geneviève MarcelinVincent CalvezFrontiers Media S.A.articleCOVID-19polyclonal antibody (PAb)SARS-CoV-2variantsneutralizationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 polyclonal antibody (PAb) SARS-CoV-2 variants neutralization Immunologic diseases. Allergy RC581-607
spellingShingle	COVID-19 polyclonal antibody (PAb) SARS-CoV-2 variants neutralization Immunologic diseases. Allergy RC581-607 Bernard Vanhove Stéphane Marot Ray T. So Benjamin Gaborit Benjamin Gaborit Gwénaëlle Evanno Isabelle Malet Guillaume Lafrogne Edwige Mevel Carine Ciron Pierre-Joseph Royer Elsa Lheriteau François Raffi François Raffi Roberto Bruzzone Roberto Bruzzone Chris Ka Pun Mok Chris Ka Pun Mok Odile Duvaux Anne-Geneviève Marcelin Vincent Calvez XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
description	Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBMs), in direct contact sites with the angiotensin converting enzyme-2 (ACE-2). Therefore, in Spike/ACE-2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study on Vero E6 cells conducted over 1 month, no mutation was associated with the addition of increasing doses of XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE-2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19) including the different variants of concern identified so far.
format	article
author	Bernard Vanhove Stéphane Marot Ray T. So Benjamin Gaborit Benjamin Gaborit Gwénaëlle Evanno Isabelle Malet Guillaume Lafrogne Edwige Mevel Carine Ciron Pierre-Joseph Royer Elsa Lheriteau François Raffi François Raffi Roberto Bruzzone Roberto Bruzzone Chris Ka Pun Mok Chris Ka Pun Mok Odile Duvaux Anne-Geneviève Marcelin Vincent Calvez
author_facet	Bernard Vanhove Stéphane Marot Ray T. So Benjamin Gaborit Benjamin Gaborit Gwénaëlle Evanno Isabelle Malet Guillaume Lafrogne Edwige Mevel Carine Ciron Pierre-Joseph Royer Elsa Lheriteau François Raffi François Raffi Roberto Bruzzone Roberto Bruzzone Chris Ka Pun Mok Chris Ka Pun Mok Odile Duvaux Anne-Geneviève Marcelin Vincent Calvez
author_sort	Bernard Vanhove
title	XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
title_short	XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
title_full	XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
title_fullStr	XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
title_full_unstemmed	XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
title_sort	xav-19, a swine glyco-humanized polyclonal antibody against sars-cov-2 spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6f9f8633566c421f939f2280d4799e1e
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XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants

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