title: Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab.
abstract: Eculizumab is indicated for the therapy of patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). Due to inhibition of terminal complement cascade, patients on eculizumab are susceptible to Neisseria meningitidis infections. The two mainstays to reduce the risk of infection are vaccination and antibiotic prophylaxis. In this retrospective study, serologic response was analyzed after vaccination with a meningococcal vaccine in 23 PNH patients (median age 36 years; range 25 - 88 years; 15 males, 8 females) by measuring serum bactericidal assay (SBA) using rabbit complement (rSBA) titers against meningococcal serogroups A, C, W, and Y. Serologic protection was defined by an rSBA titer ≥1:8. Forty-three percent (10/23) were vaccinated more than once due to chronic eculizumab treatment. Overall serologic response for the meningococcal serogroups was A: 78% (18/23), C: 87% (20/23), W: 48% (11/23), and Y: 70% (16/23). No meningococcal infections have been observed. As immunological response to vaccines varies, the use of serologic response analyses is warranted. Re-vaccination with a tetravalent conjugate vaccine under eculizumab therapy every 3 years is essential or should be based on response rates. If meningococcal infection is suspected, standby therapy with ciprofloxacin and immediate medical evaluation are recommended. The novel vaccines covering serogroup B may even further reduce the risk for infection.
authors.affiliation: Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
authors.forename: Ferras
authors.identifier: http://orcid.org/0000-0001-7530-8892
authors.initials: F
authors.lastname: Alashkar
authors.affiliation: Rheinisch-Westfälisches Institut für Wirtschaftsforschung, Essen, Germany.
authors.forename: Colin
authors.initials: C
authors.lastname: Vance
authors.affiliation: Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Herich-Terhürne
authors.affiliation: Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Preising
authors.affiliation: Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.affiliation: Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany. alexander.roeth@uk-essen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Röth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage*; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D012698:Serologic Tests / Q000379:methods; D015610:Serum Bactericidal Test / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D022401:Meningococcal Vaccines; C481642:eculizumab
keywords: Eculizumab; Meningococcal vaccination; PNH