High neutralizing potency of swine glyco‐humanized polyclonal antibodies against SARS‐CoV‐2. Issue 6 (2nd March 2021)

• Record Type: Journal Article
• Authors: Vanhove, Bernard; Duvaux, Odile; Rousse, Juliette; Royer, Pierre‐Joseph; Evanno, Gwénaëlle; Ciron, Carine; Lheriteau, Elsa; Vacher, Laurent; Gervois, Nadine; Oger, Romain; Jacques, Yannick; Conchon, Sophie; Salama, Apolline; Duchi, Roberto; Lagutina, Irina; Perota, Andrea; Delahaut, Philippe; Ledure, Matthieu; Paulus, Melody; So, Ray T.; Mok, Chris Ka‐Pun; Bruzzone, Roberto; Bouillet, Marc; Brouard, Sophie; Cozzi, Emanuele; Galli, Cesare; Blanchard, Dominique; Bach, Jean‐Marie; Soulillou, Jean‐Paul
• Is Part Of: European journal of immunology. Volume 51:Issue 6(2021)
• Page Start: 1412
• Page End: 1422
• Publication Date: 2021-03-02
• Subjects: COVID‐19 -- pig -- polyclonal antibodies -- SARS‐CoV‐2 -- spike; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202049072
• Languages: English
• ISSNs: 0014-2980

Abstract

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, 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. Abstract : GGTA1/CMAH double KO pigs produced high titers of XAV‐19, an anti‐SARS‐Cov‐2 RBD glyco‐humanized polyclonal antibody. XAV‐19 is presented with a high complement activation and a high neutralization potency in vitro and in cell‐based neutralization assays. XAV‐19 does not interact with human Fc gamma receptors, preventing Fc‐dependent enhancement or immune cells skewing.