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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Eur+J+Immunol 2021 ; 51 (6): 1412-1422 Nephropedia Template TP
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High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2 #MMPMID33576494
Vanhove B; Duvaux O; Rousse J; Royer PJ; Evanno G; Ciron C; Lheriteau E; Vacher L; Gervois N; Oger R; Jacques Y; Conchon S; Salama A; Duchi R; Lagutina I; Perota A; Delahaut P; Ledure M; Paulus M; So RT; Mok CK; Bruzzone R; Bouillet M; Brouard S; Cozzi E; Galli C; Blanchard D; Bach JM; Soulillou JP
Eur J Immunol 2021[Jun]; 51 (6): 1412-1422 PMID33576494show ga
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 alpha1,3-galactose, potentially leading to serum sickness or allergy. Here, we immunized cytidine monophosphate-N-acetylneuraminic acid hydroxylase and alpha1,3-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 alpha1,3-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 mug/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.
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Eur+J+Immunol 2021 ; 51 (6): 1412-1422
