High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2
Autor: | Dominique Blanchard, Melody Paulus, Gwénaëlle Evanno, Roberto Bruzzone, Matthieu Ledure, Sophie Brouard, Irina Lagutina, Sophie Conchon, Emanuele Cozzi, Roberto Duchi, Cesare Galli, Juliette Rousse, Bernard Vanhove, Elsa Lheriteau, Laurent Vacher, Apolline Salama, Romain Oger, Pierre-Joseph Royer, Andrea Perota, Nadine Gervois, Marc Bouillet, Yannick Jacques, Odile Duvaux, Ray T.Y. So, Jean-Marie Bach, Jean-Paul Soulillou, Chris Ka Pun Mok, Carine Ciron, Philippe Delahaut |
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Přispěvatelé: | Xenothera [Nantes, France], Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Avantea [Cremona, Italy], CER Groupe Marloie, The University of Hong Kong (HKU), University Hospital of Padua, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bpifrance, Xenothera, Société d'Accélération et Transfert de Technologie Ouest Valorisation, Région Pays de la Loire, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CER Groupe, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bernardo, Elizabeth |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
pig Swine Spike Antibodies Viral medicine.disease_cause SARS‐CoV‐2 Epitope Animals Genetically Modified chemistry.chemical_compound 0302 clinical medicine Neuraminic acid Immunology and Allergy polyclonal antibodies Research Articles Coronavirus Covid-19 SARS-CoV-2 Galactosyltransferases 3. Good health Spike Glycoprotein Coronavirus Research Article|Basic Antibody medicine.drug_class Immunology Immunity to infection Heterologous [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Monoclonal antibody Article 03 medical and health sciences Immune system [SDV.CAN] Life Sciences [q-bio]/Cancer Antigen COVID‐19 medicine Animals Humans Basic COVID-19 Serotherapy Immunization Passive Antibodies Neutralizing Virology HEK293 Cells 030104 developmental biology chemistry Polyclonal antibodies Sialic Acids biology.protein 030215 immunology |
Zdroj: | European Journal of Immunology European Journal of Immunology, Wiley-VCH Verlag, 2021, 51 (6), pp.1412-1422. ⟨10.1002/eji.202049072⟩ European Journal of Immunology, 2021, 51 (6), pp.1412-1422. ⟨10.1002/eji.202049072⟩ bioRxiv |
ISSN: | 0014-2980 1521-4141 |
Popis: | Heterologous polyclonal antibodies might represent an alternative to the use of convalescent plasma or monoclonal antibodies (mAbs) in coronavirus disease (COVID‐19) by targeting multiple antigen epitopes. However, heterologous antibodies trigger human natural xenogeneic antibody responses particularly directed against animal‐type carbohydrates, mainly the N‐glycolyl form of the neuraminic acid (Neu5Gc) and the α1,3‐galactose, potentially leading to serum sickness or allergy. Here, we immunized cytidine monophosphate‐N‐acetylneuraminic acid hydroxylase and α1,3‐galactosyl‐transferase (GGTA1) double KO pigs with the Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike receptor binding domain to produce glyco‐humanized polyclonal neutralizing antibodies lacking Neu5Gc and α1,3‐galactose epitopes. Animals rapidly developed a hyperimmune response with anti‐SARS‐CoV‐2 end‐titers binding dilutions over one to a million and end‐titers neutralizing dilutions of 1:10 000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV‐19, neutralized spike/angiotensin converting enzyme‐2 interaction at a concentration GGTA1/CMAH double KO pigs produced high titers of XAV‐19, an anti‐SARS‐Cov‐2 RBD glyco‐humanized polyclonal antibody. XAV‐19 is presented with a high complement activation and a high neutralization potency in vitro and in cell‐based neutralization assays. XAV‐19 does not interact with human Fc gamma receptors, preventing Fc‐dependent enhancement or immune cells skewing. |
Databáze: | OpenAIRE |
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