{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:33:23Z","timestamp":1793846003375,"version":"4.6.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Dysregulation of complement activation causes a number of diseases, including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. These conditions can be treated with monoclonal antibodies (mAbs) that bind to the complement component C5 and prevent formation of the membrane attack complex (MAC). While MAC is involved in uncontrolled lysis of erythrocytes in these patients, it is also required for serum bactericidal activity (SBA), i.e. clearance of encapsulated bacteria. Therefore, terminal complement blockage in these patients increases the risk of invasive disease by <jats:italic>Neisseria meningitidis<\/jats:italic> more than 1000-fold compared to the general population, despite obligatory vaccination. It is assumed that alternative instead of terminal pathway inhibition reduces the risk of meningococcal disease in vaccinated individuals. To address this, we investigated the SBA with alternative pathway inhibitors. Serum was collected from adults before and after vaccination with a meningococcal serogroup A, C, W, Y capsule conjugate vaccine and tested for meningococcal killing in the presence of factor B and D, C3, C5 and MASP-2 inhibitors. B meningococci were not included in this study since the immune response against protein-based vaccines is more complex. Unsurprisingly, inhibition of C5 abrogated killing of meningococci by all sera. In contrast, both factor B and D inhibitors affected meningococcal killing in sera from individuals with low, but not with high bactericidal anti-capsular titers. While the anti-MASP-2 mAb did not impair SBA, inhibition of C3 impeded meningococcal killing in most, but not in all sera. These data provide evidence that vaccination can provide protection against invasive meningococcal disease in patients treated with alternative pathway inhibitors.<\/jats:p>","DOI":"10.3389\/fimmu.2021.747594","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T19:30:50Z","timestamp":1633894250000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Alternative Complement Pathway Inhibition Does Not Abrogate Meningococcal Killing by Serum of Vaccinated Individuals"],"prefix":"10.3389","volume":"12","author":[{"given":"Emma","family":"Ispasanie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Muri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Schubart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Thorburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasa","family":"Zamurovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Holbro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kamm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Pluschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"B64","DOI":"10.1016\/j.vaccine.2009.04.061","article-title":"Meningococcal Carriage and Disease-Population Biology and Evolution","volume":"27","author":"Caugant","year":"2009","journal-title":"Vaccine"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090513","article-title":"Cellular and Molecular Biology of Neisseria Meningitidis Colonization and Invasive Disease","volume":"118","author":"Hill","year":"2010","journal-title":"Clin Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105033441807","article-title":"Meningococcal Disease","volume":"344","author":"Rosenstein","year":"2001","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.04.063","article-title":"Global Epidemiology of Meningococcal Disease","volume":"27","author":"Harrison","year":"2009","journal-title":"Vaccine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"98","DOI":"10.4161\/viru.26515","article-title":"Meningococcal Disease and the Complement System","volume":"5","author":"Lewis","year":"2014","journal-title":"Virulence"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00317-0","article-title":"Reduced Antibody Response to Revaccination With Meningococcal Serogroup A Polysaccharide Vaccine in Adults","volume":"19","author":"Borrow","year":"2000","journal-title":"Vaccine"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.19.1685","article-title":"Induction of Immunologic Memory by Conjugated vs Plain Meningococcal C Polysaccharide Vaccine in Toddlers: A Randomized Controlled Trial","volume":"280","author":"MacDonald","year":"1998","journal-title":"J Am Med Assoc"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1086\/515346","article-title":"Induction of Immunologic Refractoriness in Adults by Meningococcal C Polysaccharide Vaccination","volume":"178","author":"Granoff","year":"1998","journal-title":"J\u00a0Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.03.005","article-title":"Interactions Between Neisseria Meningitidis and the Complement System","volume":"15","author":"Schneider","year":"2007","journal-title":"Trends Microbiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.07.019","article-title":"Serum Bactericidal Antibody Assays - The Role of Complement in Infection and Immunity","volume":"33","author":"McIntosh","year":"2015","journal-title":"Vaccine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.129.6.1307","article-title":"Human Immunity to the Meningococcus. 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