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However, heterologous antibodies trigger human natural xenogeneic antibody responses particularly directed against animal\u2010type carbohydrates, mainly the N\u2010glycolyl form of the neuraminic acid (Neu5Gc) and the \u03b11,3\u2010galactose, potentially leading to serum sickness or allergy. Here, we immunized cytidine monophosphate\u2010N\u2010acetylneuraminic acid hydroxylase and \u03b11,3\u2010galactosyl\u2010transferase (GGTA1) double KO pigs with the Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) spike receptor binding domain to produce glyco\u2010humanized polyclonal neutralizing antibodies lacking Neu5Gc and \u03b11,3\u2010galactose epitopes. Animals rapidly developed a hyperimmune response with anti\u2010SARS\u2010CoV\u20102 end\u2010titers binding dilutions over one to a million and end\u2010titers neutralizing dilutions of 1:10\u00a0000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV\u201019, neutralized spike\/angiotensin converting enzyme\u20102 interaction at a concentration &lt;1\u00a0\u03bcg\/mL, and inhibited infection of human cells by SARS\u2010CoV\u20102 in cytopathic assays. We also found that pig GH\u2010pAb Fc domains fail to interact with human Fc receptors, thereby avoiding macrophage\u2010dependent exacerbated inflammatory responses and a possible antibody\u2010dependent enhancement. These data and the accumulating safety advantages of using GH\u2010pAbs in humans warrant clinical assessment of XAV\u201019 against COVID\u201019.<\/jats:p>","DOI":"10.1002\/eji.202049072","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T08:09:56Z","timestamp":1613290196000},"page":"1412-1422","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["High neutralizing potency of swine glyco\u2010humanized polyclonal antibodies against SARS\u2010CoV\u20102"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2872-8648","authenticated-orcid":false,"given":"Bernard","family":"Vanhove","sequence":"first","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Duvaux","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Rousse","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Joseph","family":"Royer","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gw\u00e9na\u00eblle","family":"Evanno","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Ciron","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Lheriteau","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Vacher","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Gervois","sequence":"additional","affiliation":[{"name":"Inserm CRCINA Universit\u00e9 de Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Oger","sequence":"additional","affiliation":[{"name":"Inserm CRCINA Universit\u00e9 de Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Jacques","sequence":"additional","affiliation":[{"name":"Inserm CRCINA Universit\u00e9 de Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Conchon","sequence":"additional","affiliation":[{"name":"CHU Nantes Universit\u00e9 de Nantes Inserm Centre de Recherche en Transplantation et Immunologie  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apolline","family":"Salama","sequence":"additional","affiliation":[{"name":"Xenothera  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Duchi","sequence":"additional","affiliation":[{"name":"Avantea Laboratorio di Tecnologie della Riproduzione  Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Lagutina","sequence":"additional","affiliation":[{"name":"Avantea Laboratorio di Tecnologie della Riproduzione  Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Perota","sequence":"additional","affiliation":[{"name":"Avantea Laboratorio di Tecnologie della Riproduzione  Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Delahaut","sequence":"additional","affiliation":[{"name":"CER Groupe  Marloie Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Ledure","sequence":"additional","affiliation":[{"name":"CER Groupe  Marloie Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody","family":"Paulus","sequence":"additional","affiliation":[{"name":"CER Groupe  Marloie Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray T.","family":"So","sequence":"additional","affiliation":[{"name":"HKU\u2010Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine The University of Hong Kong  Hong Kong SAR P.R. 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