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
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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