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After immunizing these mice with DNA encoding the spike protein of SARS\u2010CoV\u20102 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS\u2010CoV\u20102 spike protein. Nine antibodies neutralize SARS\u2010CoV\u20102 infection at IC50 values in the subnanomolar range. ELISA\u2010binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor\u2010binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS\u2010CoV\u20102 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS\u2010CoV\u20102\u2010induced weight loss. The two clusters of potent noncompeting SARS\u2010CoV\u20102 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID\u201019. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149374","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T05:44:03Z","timestamp":1628228643000},"page":"770-783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A pair of noncompeting neutralizing human monoclonal antibodies protecting from disease in a SARS\u2010CoV\u20102 infection model"],"prefix":"10.1002","volume":"52","author":[{"given":"Antonia Sophia","family":"Peter","sequence":"first","affiliation":[{"name":"Institute of Clinical and Molecular Virology University Hospital Erlangen Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Roth","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Internal Medicine III Nikolaus\u2010Fiebiger\u2010Center of Molecular Medicine Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian R.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Internal Medicine III Nikolaus\u2010Fiebiger\u2010Center of Molecular Medicine Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Fraedrich","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Molecular Virology University Hospital Erlangen Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobit","family":"Steinmetz","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Internal Medicine III Nikolaus\u2010Fiebiger\u2010Center of Molecular Medicine Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Damm","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Molecular Virology University Hospital Erlangen Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Hauke","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Internal Medicine III Nikolaus\u2010Fiebiger\u2010Center of Molecular Medicine Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Richel","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Molecular Virology University Hospital Erlangen Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Mueller\u2010Schmucker","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Molecular Virology University Hospital Erlangen Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Habenicht","sequence":"additional","affiliation":[{"name":"Division of Genetics Department Biology Nikolaus\u2010Fiebiger\u2010Center of Molecular Medicine Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Eberlein","sequence":"additional","affiliation":[{"name":"Department of Immunology Fraunhofer Institute for Cell Therapy and Immunology IZI  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Issmail","sequence":"additional","affiliation":[{"name":"Department of Immunology Fraunhofer Institute for Cell Therapy and Immunology IZI  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Uhlig","sequence":"additional","affiliation":[{"name":"Department of Immunology Fraunhofer Institute for Cell Therapy and Immunology IZI  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Dolles","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; 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