Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1)


SARS-CoV-2 Proteins
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    High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2

    Authors: Bernard Vanhove; Odile Duvaux; Juliette Rousse; Pierre-Joseph Royer; Gwenaelle Evanno; Carine Ciron; Elsa Lheriteau; Laurent Vacher; Nadine Gervois; Romain Oger; Yannick Jacques; Apolline Salama; Roberto Duchi; 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

    doi:10.1101/2020.07.25.217158 Date: 2020-07-25 Source: bioRxiv

    Perfusion of convalescent plasma (CP) has demonstrated a potential to improve the pneumonia MESHD induced by SARS-CoV-2, but procurement and standardization of CP are barriers to its wide usage. Heterologous polyclonal antibodies of animal origin have been used to fight against infectious agents and are a possible alternative to the use of CP in SARS-CoV-2 disease MESHD. However, 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 alpha1,3-galactose (a-Gal), ultimately forming immune complexes and potentially leading to serum sickness or allergy MESHD. To circumvent these drawbacks, we engineered animals lacking the cytidine monophosphate-N-acetylneuraminic acid hydroxylase ( CMAH HGNC) and alpha1,3-galactosyltransferase ( GGTA1 HGNC) enzymes to produce glyco-humanized polyclonal antibodies (GH-pAb) lacking Neu5Gc and a-Gal epitopes. We also found that these IgG Fc domains fail to interact with human Fc receptors and thereby should confer the safety advantage to avoiding macrophage dependent exacerbated inflammatory responses or elicit antibody-dependent enhancement (ADE), two drawbacks possibly associated with antibody responses against SARS-CoV-2. Therefore, we immunized CMAH/GGTA1 double knockout (DKO) pigs with the SARS-CoV-2 spike PROTEIN receptor binding domain (RBD) domain to elicit neutralizing antibodies. Animals rapidly developed hyperimmune sera with 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/ ACE-2 HGNC interaction at a concentration < 1microgram/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 warrant clinical assessment of XAV-19 to fight against COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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