XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 Spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants
| Autor: | 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 |
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| Přispěvatelé: | Xenothera [Nantes, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The University of Hong Kong (HKU), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Pasteur [Paris], The Chinese University of Hong Kong [Hong Kong], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), This work was supported by Xenothera, the Agence Nationale de la Recherche sur le SIDA et les Maladies Infectieuses Emergentes (ANRS MIE), AC43 Medical Virology and Emergen Program, the SARS-CoV-2 Program of the Faculty of Medicine of Sorbonne Université and by Bpifrance, grant «Projet de Recherche et Développement Structurant Pour la Compétitivité spécifique à la crise sanitaire COVD-19—POLYCOR» and the National Research Foundation of Korea (NRF) grant funded through the Korea government (NRF-2018M3A9H4055203)., We sincerely thank Prof. Xavier de Lamballerie and Dr. Franck Touret from UMR IRD 190, Inserm 1207 'Unité des Virus Émergents,' Aix-Marseille Université for their active technical contribution to generating neutralization data and for their advice. We also thank the virology departments of Saint-Antoine and Avicenne Universitary hospitals who gently shared the clinical specimen allowing us to isolate the Gamma/P.1 and Delta/B.1.617.2 variants, respectively. We also thank Prof. Jincun Zhao and Yanqun Wang for providing us the adenovirus that carries the human ACE-2, Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Předmět: |
Swine
MESH: Spike Glycoprotein Coronavirus Antibodies Viral Neutralization Epitope Epitopes Mice 0302 clinical medicine [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Immunology and Allergy MESH: COVID-19 MESH: Animals Neutralizing antibody Lung MESH: Swine Original Research MESH: Broadly Neutralizing Antibodies [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases 0303 health sciences variants [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases biology Viral Load Antigenic Variation 3. Good health 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Antigenic Variation MESH: Immunization Passive [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy MESH: Viral Load Viral load MESH: Epitopes medicine.drug_class Immunology Heterologous Antibodies Heterophile Monoclonal antibody 03 medical and health sciences medicine Animals Humans Protein Interaction Domains and Motifs MESH: Lung MESH: SARS-CoV-2 MESH: Mice COVID-19 Serotherapy 030304 developmental biology MESH: Protein Interaction Domains and Motifs MESH: Humans SARS-CoV-2 Immunization Passive COVID-19 [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy RC581-607 neutralization Virology Disease Models Animal Polyclonal antibodies biology.protein Vero cell polyclonal antibody (PAb) Immunologic diseases. Allergy MESH: Disease Models Animal Broadly Neutralizing Antibodies 030217 neurology & neurosurgery MESH: Antibodies Viral MESH: Antibodies Heterophile |
| Zdroj: | bioRxiv Frontiers in Immunology Frontiers in Immunology, Frontiers, 2021, 12, pp.761250. ⟨10.3389/fimmu.2021.761250⟩ Frontiers in Immunology, 2021, 12, pp.761250. ⟨10.3389/fimmu.2021.761250⟩ Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| DOI: | 10.1101/2021.04.02.437747 |
| Popis: | Amino acid substitutions and deletions in Spike protein of the 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 (RBM), in direct contact sites with the Angiotensin Converting Enzyme-2 (ACE-2). Therefore, in Spike/ACE2 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 with the Beta strain on Vero E6 cells conducted over 1 month, no mutation was associated with addition of increasing doses XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in a 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. |
| Databáze: | OpenAIRE |
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