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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.
Vanhove, Bernard; Marot, Stéphane; So, Ray T; Gaborit, Benjamin; Evanno, Gwénaëlle; Malet, Isabelle; Lafrogne, Guillaume; Mevel, Edwige; Ciron, Carine; Royer, Pierre-Joseph; Lheriteau, Elsa; Raffi, François; Bruzzone, Roberto; Mok, Chris Ka Pun; Duvaux, Odile; Marcelin, Anne-Geneviève; Calvez, Vincent.
  • Vanhove B; Xenothera, Nantes, France.
  • Marot S; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Department of Virology, Paris, France.
  • So RT; Hong Kong University (HKU)-Pasteur Research Pole, School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
  • Gaborit B; Department of Infectious Disease, Nantes University Hospital, Nantes, France.
  • Evanno G; Institut National de la Santé et de la Recherche Médicale (INSERM) CIC1413, Nantes University Hospital, Nantes, France.
  • Malet I; Xenothera, Nantes, France.
  • Lafrogne G; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Department of Virology, Paris, France.
  • Mevel E; Xenothera, Nantes, France.
  • Ciron C; Xenothera, Nantes, France.
  • Royer PJ; Xenothera, Nantes, France.
  • Lheriteau E; Xenothera, Nantes, France.
  • Raffi F; Xenothera, Nantes, France.
  • Bruzzone R; Department of Infectious Disease, Nantes University Hospital, Nantes, France.
  • Mok CKP; Institut National de la Santé et de la Recherche Médicale (INSERM) CIC1413, Nantes University Hospital, Nantes, France.
  • Duvaux O; Hong Kong University (HKU)-Pasteur Research Pole, School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
  • Marcelin AG; Department of Cell Biology and Infection, Institut Pasteur, Paris, France.
  • Calvez V; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Immunol ; 12: 761250, 2021.
Article in English | MEDLINE | ID: covidwho-1556220
Preprint
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Heterophile / Spike Glycoprotein, Coronavirus / Broadly Neutralizing Antibodies / SARS-CoV-2 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Variants Limits: Animals / Humans Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.761250

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Heterophile / Spike Glycoprotein, Coronavirus / Broadly Neutralizing Antibodies / SARS-CoV-2 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Variants Limits: Animals / Humans Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.761250