Multi‐component meningococcal serogroup B (MenB)‐4C vaccine induces effective opsonophagocytic killing in children with a complement deficiency

• Published in: Clinical and experimental immunology 2019-12, Vol.198 (3), p.381-389
• Main Authors: van den Broek, B., Els, C. A. C. M., Kuipers, B., Aerde, K., Henriet, S. S., Groot, R., Jonge, M. I., Langereis, J. D., Flier, M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alternative pathway; Antibodies, Bacterial - immunology; Assaying; Bactericidal activity; Child; Children; Complement deficiency; Complement factor H; Complement Factor H - immunology; Complement Factor H - metabolism; complement‐deficient; Female; Heparin; Hereditary Complement Deficiency Diseases - immunology; Hereditary Complement Deficiency Diseases - microbiology; Hereditary Complement Deficiency Diseases - therapy; Humans; Immunization; Immunogenicity; Lysis; Male; Membrane vesicles; MenB‐4C; Meningitis, Meningococcal - immunology; Meningitis, Meningococcal - microbiology; Meningitis, Meningococcal - therapy; Meningococcal Vaccines - administration & dosage; Meningococcal Vaccines - immunology; Neisseria meningitidis; Neisseria meningitidis, Serogroup B - immunology; Neisseria meningitidis, Serogroup B - physiology; Opsonin Proteins - immunology; Opsonin Proteins - metabolism; Original; Pathogens; Phagocytosis - immunology; Proteins; Serum bactericidal activity; Vaccination; vaccine; Vaccines
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/cei.13368

Summary Vaccination against meningococcal serogroup B is recommended for patients with a complement deficiency; however, although immunogenicity in this patient group has been shown, efficacy has not yet been established. In this study, we collected serum from children with a complement deficiency in the alternative pathway or in late terminal pathway before and after vaccination with multi‐component meningococcal serogroup B (MenB)‐4C. MenB‐4C is a multi‐component, protein‐based vaccine against MenB consisting of factor H‐binding protein, Neisserial heparin‐binding protein, Neisserial adhesion A and outer membrane vesicles containing Porin A. We assessed the vaccine immunogenicity and vaccine‐mediated protection by a whole cell enzyme‐linked immunosorbent assay with Neisseria meningitidis serogroup B strains H44/76, 5/99 and NZ98/254, which shows that vaccination induced antibody titers against meningococcus. We show that the classical serum bactericidal activity assay with exogenous serum indicates the presence of vaccine‐induced antibodies and capacity to activate complement‐mediated pathogen lysis. However, in children with a late terminal pathway deficiency, no complement‐mediated pathogen lysis was observed when autologous serum was applied in the serum bactericidal activity assay, demonstrating a lack of serum bactericidal activity in children with complement deficiencies. However, MenB‐4C vaccination still induced effective complement‐dependent opsonophagocytic killing against N. meningitidis serogroup B in reconstituted whole blood with autologous serum from children with an alternative pathway or late terminal pathway deficiency. These findings support the recommendation to vaccinate all complement‐deficient children against MenB. Patients with a complement deficiency are extensively vaccinated against Meningococcal infection, including with the 4C‐MenB vaccine against N. meningitidis serogroup B. We show that vaccination induces functional antibodies, but does not result in bacterial killing via the complement system in patients with a late terminal pathway deficiency. Despite the complement deficiency, killing can occur via opsonophagocytosis.