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

Eur J Immunol. 2021 Jun;51(6):1412-1422. doi: 10.1002/eji.202049072. Epub 2021 Mar 2.


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 <1 μg/mL, and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. We also found that pig GH-pAb Fc domains fail to interact with human Fc receptors, thereby avoiding macrophage-dependent exacerbated inflammatory responses and a possible antibody-dependent enhancement. These data and the accumulating safety advantages of using GH-pAbs in humans warrant clinical assessment of XAV-19 against COVID-19.

Keywords: COVID-19; SARS-CoV-2; pig; polyclonal antibodies; spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / immunology
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / pharmacology
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 / therapy*
  • COVID-19 Serotherapy
  • Galactosyltransferases / deficiency
  • Galactosyltransferases / immunology
  • HEK293 Cells
  • Humans
  • Immunization, Passive
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Sialic Acids / genetics
  • Sialic Acids / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Swine


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • N-(O-acetyl)glycoloylneuraminic acid
  • Sialic Acids
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Galactosyltransferases
  • alpha-1,3-galactosyltransferase 1, porcine