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High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2
Bernard Vanhove; Odile Duvaux; Juliette Rousse; Pierre-Joseph Royer; Gwenaelle Evanno; Carine Ciron; Elsa Lheriteau; Laurent Vacher; Nadine Gervois; Romain Oger; Yannick Jacques; Sophie Conchon; Apolline Salama; Roberto Duchi; Irina Lagutina; Andrea Perota; Philippe Delahaut; Matthieu Ledure; Melody Paulus; Ray So; Chris Ka Pun Mok; Roberto Bruzzone; Marc Bouillet; Sophie Brouard; Emanuele Cozzi; Cesare Galli; Dominique Blanchard; Jean-Marie Bach; Jean-Paul Soulillou.
Affiliation
  • Bernard Vanhove; Xenothera
  • Odile Duvaux; Xenothera
  • Juliette Rousse; Xenothera
  • Pierre-Joseph Royer; Xenothera
  • Gwenaelle Evanno; Xenothera
  • Carine Ciron; Xenothera
  • Elsa Lheriteau; Xenothera
  • Laurent Vacher; Xenothera
  • Nadine Gervois; University of Nantes
  • Romain Oger; University of Nantes
  • Yannick Jacques; University of Nantes
  • Sophie Conchon; University of Nantes
  • Apolline Salama; University of Nantes
  • Roberto Duchi; Avantea
  • Irina Lagutina; Avantea
  • Andrea Perota; University of Nantes
  • Philippe Delahaut; CER Groupe
  • Matthieu Ledure; CER Groupe
  • Melody Paulus; CER Groupe
  • Ray So; The University of Hong Kong
  • Chris Ka Pun Mok; The University of Hong Kong
  • Roberto Bruzzone; The University of Hong Kong
  • Marc Bouillet; Xenothera
  • Sophie Brouard; University of Nantes
  • Emanuele Cozzi; Padua University Hospital
  • Cesare Galli; Avantea
  • Dominique Blanchard; Xenothera
  • Jean-Marie Bach; Oniris
  • Jean-Paul Soulillou; University of Nantes
Preprint in English | bioRxiv | ID: ppbiorxiv-217158
Journal article
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ABSTRACT
Perfusion of convalescent plasma (CP) has demonstrated a potential to improve the pneumonia induced by SARS-CoV-2, but procurement and standardization of CP are barriers to its wide usage. Many monoclonal antibodies (mAbs) have been developed but appear insufficient to neutralize SARS-CoV-2 unless two or three of them are being combined. Therefore, heterologous polyclonal antibodies of animal origin, that have been used for decades to fight against infectious agents might represent a highly efficient alternative to the use of CP or mAbs in COVID-19 by targeting multiple antigen epitopes. However, conventional heterologous polyclonal antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrate epitopes, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the Gal 1,3-galactose (Gal), ultimately forming immune complexes and potentially leading to serum sickness or allergy. To circumvent these drawbacks, we engineered animals lacking the genes coding for the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) and 1,3-galactosyl-transferase (GGTA1) enzymes to produce glyco-humanized polyclonal antibodies (GH-pAb) lacking Neu5Gc and -Gal epitopes. We found that pig IgG Fc domains fail to interact with human Fc receptors and thereby should confer the safety advantage to avoiding macrophage dependent exacerbated inflammatory responses, a drawback possibly associated with antibody responses against SARS-CoV-2 or to avoiding a possible antibody-dependent enhancement (ADE). Therefore, we immunized CMAH/GGTA1 double knockout (DKO) pigs with the SARS-CoV-2 spike receptor-binding domain (RBD) to elicit neutralizing antibodies. 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 110,000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized Spike/angiotensin converting enzyme-2 (ACE-2) interaction at a concentration < 1g/mL and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. These data and the accumulating safety advantages of using glyco-humanized swine antibodies in humans warranted clinical assessment of XAV-19 to fight against COVID-19.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2020 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2020 Document type: Preprint
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