title: A multi-component meningococcal serogroup B vaccine (4CMenB): the clinical development program.
abstract: Recently approved in Europe and Australia, the multi-component meningococcal B vaccine, 4CMenB (Bexsero®, Novartis Vaccines and Diagnostics), contains three surface-exposed recombinant proteins (fHbp, NadA, and NHBA) and New Zealand strain outer membrane vesicles (NZ OMV) with PorA 1.4 antigenicity. This comprehensive review of the 4CMenB clinical development program covers pivotal phase I/IIb/III studies in over 7,000 adults, adolescents, and infants. The immunological correlate for clinical protection used was human complement-mediated serum bactericidal activity titers ≥4 or 5 against indicator strains for individual antigens. Based on achievement of protective titers, a four-dose schedule (three primary doses and one booster dose) for infants and a two-dose schedule for adolescents provided the best results. Observed increases in injection site pain/tenderness and fever in infants, and injection site pain, malaise, and headache in adolescents compared with routine vaccines, were mostly mild to moderate; frequencies of rare events (Kawasaki disease, juvenile arthritis) were not significantly different from non-vaccinated individuals. 4CMenB is conservatively estimated to provide 66-91 % coverage against meningococcal serogroup B strains worldwide.
authors: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Avda Independencia 1027, Santiago, Chile, moryan@med.uchile.cl.
authors: Miguel
authors: M
authors: O'Ryan
authors: Jeffrey
authors: J
authors: Stoddard
authors: Daniela
authors: D
authors: Toneatto
authors: James
authors: J
authors: Wassil
authors: Peter M
authors: PM
authors: Dull
mesh_terms: D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C570015:4CMenB vaccine; D022401:Meningococcal Vaccines