tetano
Editor, Senior Moderator
Front Immunol
. 2021 Nov 15;12:761250.
doi: 10.3389/fimmu.2021.761250. eCollection 2021.
XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
Bernard Vanhove[SUP] 1 [/SUP], Stéphane Marot[SUP] 2 [/SUP], Ray T So[SUP] 3 [/SUP], Benjamin Gaborit[SUP] 4 5 [/SUP], Gwénaëlle Evanno[SUP] 1 [/SUP], Isabelle Malet[SUP] 2 [/SUP], Guillaume Lafrogne[SUP] 1 [/SUP], Edwige Mevel[SUP] 1 [/SUP], Carine Ciron[SUP] 1 [/SUP], Pierre-Joseph Royer[SUP] 1 [/SUP], Elsa Lheriteau[SUP] 1 [/SUP], François Raffi[SUP] 4 5 [/SUP], Roberto Bruzzone[SUP] 3 6 [/SUP], Chris Ka Pun Mok[SUP] 7 8 [/SUP], Odile Duvaux[SUP] 1 [/SUP], Anne-Geneviève Marcelin[SUP] 2 [/SUP], Vincent Calvez[SUP] 2 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; neutralization; polyclonal antibody (PAb); variants.
. 2021 Nov 15;12:761250.
doi: 10.3389/fimmu.2021.761250. eCollection 2021.
XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants
Bernard Vanhove[SUP] 1 [/SUP], Stéphane Marot[SUP] 2 [/SUP], Ray T So[SUP] 3 [/SUP], Benjamin Gaborit[SUP] 4 5 [/SUP], Gwénaëlle Evanno[SUP] 1 [/SUP], Isabelle Malet[SUP] 2 [/SUP], Guillaume Lafrogne[SUP] 1 [/SUP], Edwige Mevel[SUP] 1 [/SUP], Carine Ciron[SUP] 1 [/SUP], Pierre-Joseph Royer[SUP] 1 [/SUP], Elsa Lheriteau[SUP] 1 [/SUP], François Raffi[SUP] 4 5 [/SUP], Roberto Bruzzone[SUP] 3 6 [/SUP], Chris Ka Pun Mok[SUP] 7 8 [/SUP], Odile Duvaux[SUP] 1 [/SUP], Anne-Geneviève Marcelin[SUP] 2 [/SUP], Vincent Calvez[SUP] 2 [/SUP]
Affiliations
- PMID: 34868003
- PMCID: PMC8634597
- DOI: 10.3389/fimmu.2021.761250
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; neutralization; polyclonal antibody (PAb); variants.