{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:28:18Z","timestamp":1785241698584,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Over the last decade there has been an explosion in complement therapies; one\u2010third of the drugs in the clinic or in development target C5 protein. Eculizumab, a monoclonal antibody (mAb) that binds C5 and blocks its cleavage by the convertase, is the current reference standard treatment for atypical haemolytic uraemic syndrome (aHUS) and paroxysmal nocturnal haemoglobinuria (PNH) and in clinical trials for many other diseases. Here we describe a panel of novel anti\u2010C5 mAb, including mAb that, like Eculizumab, are efficient inhibitors of complement but, unlike Eculizumab, inhibit across species, including human, rat, rabbit and guinea pig. Several inhibitory anti\u2010C5 mAb were identified and characterized for C5 binding and lytic inhibitory capacity in comparison to current therapeutic anti\u2010C5 mAb; three clones, 4G2, 7D4 and 10B6, were selected and further characterized for ligand specificity and affinity and cross\u2010species inhibitory activity. The mAb 10B6 was human\u2010specific whereas mAb 4G2 and 7D4 efficiently inhibited lysis by human, rabbit and rat serum, and weakly inhibited guinea pig complement; 7D4 also weakly inhibited mouse complement <jats:italic>in vitro<\/jats:italic> The rat C5\u2010cross\u2010reactive mAb 4G2, when administered intraperitoneally in a rat model of myasthenia gravis, effectively blocked the disease and protected muscle endplates from destruction. To our knowledge this is the first report of an anti\u2010C5 function blocking mAb that permits preclinical studies in rats.<\/jats:p>","DOI":"10.1111\/imm.13083","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T18:49:18Z","timestamp":1558637358000},"page":"283-295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Development and characterization of novel anti\u2010C5 monoclonal antibodies capable of inhibiting complement in multiple species"],"prefix":"10.1111","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-3550","authenticated-orcid":false,"given":"Wioleta M.","family":"Zelek","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity School of Medicine Systems Immunity Research Institute Cardiff University Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity School of Medicine Systems Immunity Research Institute Cardiff University Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Paul","family":"Morgan","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity School of Medicine Systems Immunity Research Institute Cardiff University Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.04.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113810"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12952"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4657"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110189"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501536102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110359"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109557"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1344"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061648"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094136"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2013.05.224"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.06.008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0655-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v19.i3.10"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0301019"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01087-7"},{"key":"e_1_2_9_19_1","first-page":"86136","article-title":"Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study","volume":"9","author":"Lee JW","year":"2018","journal-title":"Blood"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195909"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12982"},{"key":"e_1_2_9_22_1","first-page":"2453","article-title":"Continuous cultures of fused cells secreting antibody of predefined specificity","volume":"174","author":"K\u00f6hler G","year":"1975","journal-title":"J Immunol"},{"key":"e_1_2_9_23_1","first-page":"295","article-title":"C6 polymorphism and C6 deficiency in site strains of the mutation\u2010prone Peru\u2010Coppock mice","volume":"6","author":"Orren A","year":"1989","journal-title":"Comp Inflamm"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2018.07.016"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512438238"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03198.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03205.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0875-9"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2018.0110"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0662-9"},{"key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1182\/blood.V126.23.939.939","article-title":"Preclinical evaluation of RA101495, a potent cyclic peptide inhibitor of C5 for the treatment of paroxysmal nocturnal hemoglobinuria","volume":"126","author":"Ricardo A","year":"2015","journal-title":"Blood"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.04070.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03561.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8562"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600280"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2016.07.016"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3196"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402956"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(00)80099-6"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198612000-00014"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13083","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.13083","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T06:38:38Z","timestamp":1694327918000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,17]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1111\/imm.13083"],"URL":"https:\/\/doi.org\/10.1111\/imm.13083","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,17]]},"assertion":[{"value":"2019-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}