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Journal Articles European Journal of Immunology Year : 2021

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

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Bernard Vanhove
  • Function : Correspondent author
  • PersonId : 1109210

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Philippe Delahaut
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Matthieu Ledure
  • Function : Author
Melody Paulus
  • Function : Author

Abstract

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 α1,3galactose, 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 antibodydependent enhancement. These data and the accumulating safety advantages of using GH-pAbs in humans warrant clinical assessment of XAV-19 against COVID-19.
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Dates and versions

inserm-03333751 , version 1 (03-09-2021)

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Bernard Vanhove, Odile Duvaux, Juliette Rousse, Pierre‐joseph Royer, Gwénaëlle Evanno, et al.. High neutralizing potency of swine glyco‐humanized polyclonal antibodies against SARS‐CoV‐2. European Journal of Immunology, 2021, 51 (6), pp.1412 - 1422. ⟨10.1002/eji.202049072⟩. ⟨inserm-03333751⟩
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