title: Antibody avidity and immunoglobulin G isotype distribution following immunization with a monovalent meningococcal B outer membrane vesicle vaccine.
abstract: The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.
authors.affiliation: Laboratory for Vaccine Research. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. clementien.vermont@rivm.nl
authors.forename: C L
authors.initials: CL
authors.lastname: Vermont
authors.forename: H H
authors.initials: HH
authors.lastname: van Dijken
authors.forename: C J P
authors.initials: CJ
authors.lastname: van Limpt
authors.forename: R
authors.initials: R
authors.lastname: de Groot
authors.forename: L
authors.initials: L
authors.lastname: van Alphen
authors.forename: G P J M
authors.initials: GP
authors.lastname: van Den Dobbelsteen
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000145:classification / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology*; D016667:Bacterial Capsules; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000145:classification / Q000276:immunology; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D018272:Porins / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018272:Porins; D014614:Vaccines, Synthetic; C039455:capsular polysaccharide, meningococcal group B; C057699:porin protein, Neisseria