Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer membrane vesicle vaccine MenBvac

ABSTRACT The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.

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Antibody Avidity and Immunoglobulin G Isotype Distribution following Immunization with a Monovalent Meningococcal B Outer Membrane Vesicle Vaccine

Infection and Immunity ◽

10.1128/iai.70.2.584-590.2002 ◽

2002 ◽

Vol 70 (2) ◽

pp. 584-590 ◽

Cited By ~ 55

Author(s):

C. L. Vermont ◽

H. H. van Dijken ◽

C. J. P. van Limpt ◽

R. de Groot ◽

L. van Alphen ◽

...

Keyword(s):

Outer Membrane ◽

Immunoglobulin G ◽

Protective Immunity ◽

Membrane Vesicle ◽

Booster Vaccination ◽

Phase Iii ◽

Enzyme Linked Immunosorbent Assay ◽

Outer Membrane Vesicle ◽

Before And After ◽

Avidity Maturation

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 AlPO4 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.

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Outer membrane vesicle of Neisseria meningitidis serogroup B as an adjuvant in immunization of rabbit against Neisseria meningitidis serogroup A

African Journal of Microbiology Research ◽

10.5897/ajmr11.361 ◽

2011 ◽

Vol 5 (19) ◽

pp. 3090-3095 ◽

Cited By ~ 5

Author(s):

Davar Siadat Seyed ◽

Reza Naddaf Saied ◽

Zangeneh Mehrangiz ◽

Moshiri Arfa ◽

Mehdi Sadat Seyed ◽

...

Keyword(s):

Neisseria Meningitidis ◽

Outer Membrane ◽

Membrane Vesicle ◽

Outer Membrane Vesicle

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Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00070-12 ◽

2012 ◽

Vol 19 (5) ◽

pp. 659-665 ◽

Cited By ~ 15

Author(s):

Elizabeth E. Moran ◽

Robert Burden ◽

Joseph E. Labrie ◽

Zhiyun Wen ◽

Xin-Min Wang ◽

...

Keyword(s):

Antibody Response ◽

Neisseria Meningitidis ◽

Outer Membrane ◽

Bactericidal Activity ◽

Membrane Vesicle ◽

Small Sample ◽

Outer Membrane Vesicle ◽

Content Type ◽

Bactericidal Antibody ◽

Membrane Antigens

ABSTRACTRabbit immunogenicity studies on an experimental trivalent native outer membrane vesicle vaccine derived from three serogroup B strains were conducted to evaluate the effectiveness of this vaccine at inducing an antibody response with serum bactericidal activity against meningococcal strains of other serogroups in addition to serogroup B strains. The results showed that the vaccine was capable of inducing an effective broad-based bactericidal antibody response in rabbits against a small sample ofNeisseria meningitidisstrains of serogroups C, W135, and X and, to a lesser extent, serogroups A and Y. Analysis of antibody specificity using a bactericidal depletion assay revealed that antibodies to lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental trivalent outer membrane vesicle vaccine were responsible for most of the bactericidal activity against strains of the otherN. meningitidisserogroups. In the case of serogroup AN. meningitidisstrains, the outer membrane antigen NadA was primarily responsible for protection. The outer membrane antigens fHbp and OpcA were also effective in removing some bactericidal activity from the sera.

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Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

PLoS ONE ◽

10.1371/journal.pone.0054314 ◽

2013 ◽

Vol 8 (1) ◽

pp. e54314 ◽

Cited By ~ 33

Author(s):

Bas van de Waterbeemd ◽

Gijsbert Zomer ◽

Jan van den IJssel ◽

Lonneke van Keulen ◽

Michel H. Eppink ◽

...

Keyword(s):

Oxidative Stress ◽

Neisseria Meningitidis ◽

Outer Membrane ◽

Vaccine Development ◽

Membrane Vesicle ◽

Outer Membrane Vesicle ◽

Vesicle Release

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Functional Activities and Epitope Specificity of Human and Murine Antibodies against the Class 4 Outer Membrane Protein (Rmp) of Neisseria meningitidis

Infection and Immunity ◽

10.1128/iai.67.3.1267-1276.1999 ◽

1999 ◽

Vol 67 (3) ◽

pp. 1267-1276 ◽

Cited By ~ 38

Author(s):

Einar Rosenqvist ◽

Alexis Musacchio ◽

Audun Aase ◽

E. Arne Høiby ◽

Ellen Namork ◽

...

Keyword(s):

Membrane Protein ◽

Neisseria Meningitidis ◽

Outer Membrane ◽

Outer Membrane Protein ◽

Membrane Vesicle ◽

Bactericidal Effect ◽

Outer Membrane Vesicle ◽

Human Sera ◽

High Concentrations ◽

Group B

ABSTRACT Antibodies against the class 4 outer membrane protein (OMP) fromNeisseria meningitidis have been purified from sera from vaccinees immunized with the Norwegian meningococcal group B outer membrane vesicle vaccine. The human sera and purified antibodies reacted strongly with the class 4 OMP in immunoblots, whereas experiments with whole bacteria showed only weak reactions, indicating that the antibodies mainly reacted with parts of the class 4 molecule that were not exposed. The purified human anti-class 4 OMP antibodies and the monoclonal antibodies (MAbs) were neither bactericidal nor opsonic against live meningococci. Three new MAbs against the class 4 OMP were generated and compared with other, previously described MAbs. Three linear epitopes in different regions of the class 4 OMP were identified by the reaction of MAbs with synthetic peptides. The MAbs showed no blocking effect on bactericidal activity of MAbs against other OMPs. However, one of the eight purified human anti-class 4 OMP antibody preparations, selected from immunoblot reactions among sera from 27 vaccinees, inhibited at high concentrations the bactericidal effect of a MAb against the class 1 OMP. However, these antibodies were not vaccine induced, as they were present also before vaccination. Therefore, this study gave no evidence that vaccination with a meningococcal outer membrane vesicle vaccine containing the class 4 OMP induces blocking antibodies. Our data indicated that the structure of class 4 OMP does not correspond to standard β-barrel structures of integral OMPs and that no substantial portion of the OmpA-like C-terminal region of this protein is located at the surface of the outer membrane.

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