{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:54:20Z","timestamp":1794002060283,"version":"4.8.0"},"reference-count":22,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Complement C5 inhibitor eculizumab has a great impact on the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). However, this treatment success has a major drawback: a substantially increased susceptibility for life-threatening Neisseria meningitidis infections. Therefore, N meningitidis vaccination is strongly advised before initiating complement C5\u2013blocking therapy. In this study, we show that the multicomponent N meningitidis serogroup B (4CMenB) vaccination of PNH patients treated with eculizumab results in a significant increase in anti\u2013N\u00a0meningitidis serogroup B (MenB) plasma immunoglobulin G (IgG) levels. Anti-MenB IgG was able to bind to the bacterial surface and initiate complement activation; however, inhibition of the membrane attack complex formation completely blocked whole blood\u2013mediated killing of MenB. This would suggest that, despite 4CMenB vaccination, PNH patients taking C5 inhibitors are not sufficiently protected against MenB infection, which is in line with the fact that vaccinated PNH patients still experience meningococcal infections.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002497","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T16:35:15Z","timestamp":1596818115000},"page":"3615-3620","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":48,"title":["Eculizumab impairs Neisseria meningitidis serogroup B killing in whole blood despite 4CMenB vaccination of PNH patients"],"prefix":"10.1182","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-3202","authenticated-orcid":false,"given":"Jeroen D.","family":"Langereis","sequence":"first","affiliation":[{"name":"Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences,"},{"name":"Laboratory of Medical Immunology, Department of Laboratory Medicine,"},{"name":"Radboud Center for Infectious Diseases, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-4788","authenticated-orcid":false,"given":"Bryan","family":"van den Broek","sequence":"additional","affiliation":[{"name":"Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences,"},{"name":"Radboud Center for Infectious Diseases, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd","family":"Franssen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2950-4977","authenticated-orcid":false,"given":"Irma","family":"Joosten","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Immunology, Department of Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1801-2072","authenticated-orcid":false,"given":"Nicole M. A.","family":"Blijlevens","sequence":"additional","affiliation":[{"name":"Department of Hematology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2812-5895","authenticated-orcid":false,"given":"Marien I.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences,"},{"name":"Radboud Center for Infectious Diseases, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-0800","authenticated-orcid":false,"given":"Saskia","family":"Langemeijer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"issue":"12","key":"2020080711342604800_B1","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1056\/NEJMoa061648","article-title":"The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria","volume":"355","author":"Hillmen","year":"2006","journal-title":"N Engl J Med"},{"issue":"6","key":"2020080711342604800_B2","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1182\/blood-2018-09-876805","article-title":"Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study","volume":"133","author":"Kulasekararaj","year":"2019","journal-title":"Blood"},{"issue":"6","key":"2020080711342604800_B3","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2018-09-876136","article-title":"Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study","volume":"133","author":"Lee","year":"2019","journal-title":"Blood"},{"issue":"2","key":"2020080711342604800_B4","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/bjh.15790","article-title":"Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis","volume":"185","author":"Soci\u00e9","year":"2019","journal-title":"Br J Haematol"},{"key":"2020080711342604800_B5","unstructured":"Centers for Disease Control and Prevention\n          . Managing the risk of meningococcal disease among patients who receive complement inhibitor therapy.https:\/\/www.cdc.gov\/meningococcal\/clinical\/eculizumab.html. Accessed 1 February 2020."},{"key":"2020080711342604800_B6","unstructured":"US Food and Drug Administration\n          . Soliris (eculizumab) product label. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/125166s417lbl.pdf. Accessed 1 February 2020."},{"key":"2020080711342604800_B7","unstructured":"US Food and Drug Administration\n          . Ultomiris (ravulizumab) product label. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761108s000lbl.pdf. Accessed 1 February 2020."},{"issue":"7","key":"2020080711342604800_B8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1182\/blood-2017-05-781450","article-title":"Eculizumab treatment and impaired opsonophagocytic killing of meningococci by whole blood from immunized adults","volume":"130","author":"Konar","year":"2017","journal-title":"Blood"},{"issue":"2","key":"2020080711342604800_B9","first-page":"139","article-title":"Meningococcal strains isolated from teenage patients during the serogroup B vaccination trial in Norway: serotyping, serosubtyping, immunotyping and clonal analysis","volume":"14","author":"Fr\u00f8holm","year":"1991","journal-title":"NIPH Ann"},{"issue":"1","key":"2020080711342604800_B10","doi-asserted-by":"crossref","first-page":"e00430","DOI":"10.1128\/CVI.00430-16","article-title":"Serum bactericidal antibody responses of adults immunized with the MenB-4C vaccine against genetically diverse serogroup B meningococci","volume":"24","author":"Giuntini","year":"2017","journal-title":"Clin Vaccine Immunol"},{"issue":"3","key":"2020080711342604800_B11","first-page":"177","article-title":"Typing of group-B Neisseria meningitidis with monoclonal antibodies in the whole-cell ELISA","volume":"26","author":"Abdillahi","year":"1988","journal-title":"J Med Microbiol"},{"issue":"17-18","key":"2020080711342604800_B12","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1016\/j.vaccine.2005.01.051","article-title":"Meningococcal surrogates of protection\u2013serum bactericidal antibody activity","volume":"23","author":"Borrow","year":"2005","journal-title":"Vaccine"},{"issue":"1","key":"2020080711342604800_B13","doi-asserted-by":"crossref","first-page":"42137","DOI":"10.1038\/srep42137","article-title":"A versatile assay to determine bacterial and host factors contributing to opsonophagocytotic killing in hirudin-anticoagulated whole blood","volume":"7","author":"van der Maten","year":"2017","journal-title":"Sci Rep"},{"issue":"3","key":"2020080711342604800_B14","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/cei.13368","article-title":"Multi-component meningococcal serogroup B (MenB)-4C vaccine induces effective opsonophagocytic killing in children with a complement deficiency","volume":"198","author":"van den Broek","year":"2019","journal-title":"Clin Exp Immunol"},{"issue":"37","key":"2020080711342604800_B15","doi-asserted-by":"crossref","first-page":"15861","DOI":"10.1073\/pnas.0903613106","article-title":"Human genetic deficiencies reveal the roles of complement in the inflammatory network: lessons from nature","volume":"106","author":"Lappeg\u00e5rd","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"8","key":"2020080711342604800_B16","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/fty086","article-title":"Differential influences of complement on neutrophil responses to Neisseria meningitidis infection","volume":"76","author":"Kr\u00fcger","year":"2018","journal-title":"Pathog Dis"},{"issue":"4","key":"2020080711342604800_B17","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1128\/CVI.00666-15","article-title":"Cellular immune responses in humans induced by two serogroup B meningococcal outer membrane vesicle vaccines given separately and in combination","volume":"23","author":"Oftung","year":"2016","journal-title":"Clin Vaccine Immunol"},{"issue":"5","key":"2020080711342604800_B18","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1086\/590669","article-title":"Mucosal immunity in healthy adults after parenteral vaccination with outer-membrane vesicles from Neisseria meningitidis serogroup B","volume":"198","author":"Davenport","year":"2008","journal-title":"J Infect Dis"},{"key":"2020080711342604800_B19","article-title":"Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria [published online ahead of print 16 Jan 2020]","author":"Brodsky","journal-title":"Haematologica"},{"issue":"27","key":"2020080711342604800_B20","doi-asserted-by":"crossref","first-page":"734","DOI":"10.15585\/mmwr.mm6627e1","article-title":"High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine","volume":"66","author":"McNamara","year":"2017","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2020080711342604800_B21","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.cmi.2018.02.002","article-title":"ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors)","volume":"24","author":"Winthrop","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2020080711342604800_B22","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1182\/blood-2019-127005","article-title":"Prophylactic antibiotic use and risk of meningococcal infections in patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab who received meningococcal vaccination: results from the International PNH Registry","volume":"134","author":"Patriquin","year":"2019","journal-title":"Blood"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/4\/15\/3615\/1751780\/advancesadv2020002497.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/4\/15\/3615\/1751780\/advancesadv2020002497.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T16:35:42Z","timestamp":1596818142000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/4\/15\/3615\/461714\/Eculizumab-impairs-Neisseria-meningitidis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":22,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2020,8,11]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020002497","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]}}}