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

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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https://www.hal.inserm.fr/inserm-03333751
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Friday, September 3, 2021 - 11:11:48 AM
Last modification on : Tuesday, May 24, 2022 - 2:27:47 PM
Long-term archiving on: : Saturday, December 4, 2021 - 6:50:26 PM

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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, Wiley-VCH Verlag, 2021, 51 (6), pp.1412 - 1422. ⟨10.1002/eji.202049072⟩. ⟨inserm-03333751⟩

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