Immune Responses against Major Outer Membrane Antigens of Neisseria meningitidis in Vaccinees and Controls Who Contracted Meningococcal Disease during the Norwegian Serogroup B Protection Trial (original) (raw)
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FEMS Immunology & Medical Microbiology, 2000
We evaluated the bactericidal antibody response to Neisseria meningitidis serogroup B in convalescent patients (n = 65) from bacterial meningitis. Patients infected with B meningococci were stratified according to their vaccination status (Cuban BC vaccine) into group 1 (immunized) (n = 12) and group 2 (non-immunized) (n = 15). The results suggested that antibody titers v 2 (log 2 ) indicate a specific immune response to N. meningitidis. In group 1, 64% of patients had a significant antibody titer (v 2) in their acute sera against a B:4:P1.15 strain, compared to only 21% of group 2 patients. All patients from group 1 without bactericidal antibodies in their acute sera had a significant increase (at least 2-fold increase in log 2 titers) in antibody titers in their convalescent sera, in contrast, to only 27% of patients from group 2 (P = 0.06). Using mutant strains lacking OMP1 or OMP5, it was shown that OMP1 was an important antigen recognized by immunized patients but not by non-immunized patients. ß 2000 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.
Infection and Immunity, 2007
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.
Clinical and Vaccine Immunology, 2004
Meningococcal serogroup-specific immunoglobulin G (IgG), IgG1, and IgG2 concentrations were assigned to three reference sera, CDC 1992, 89-SF, and 96/562, for meningococcal serogroups A, C, Y, and W135 via the method of cross standardization. The sum of the serogroup-specific IgG1 and IgG2 concentrations determined for the four meningococcal serogroups showed good agreement with the serogroup-specific IgG either determined here or as previously represented. Following the assignment of meningococcal serogroup-specific IgG1 and IgG2 concentration to these reference sera, a meningococcal serogroup-specific IgG1 and IgG2 enzymelinked immunosorbent assay protocol was developed. The serogroup A and C specific subclass distribution of a panel of adult sera collected following vaccination with any combination of meningococcal serogroup C conjugate, bivalent, or tetravalent polysaccharide vaccines was determined. For the determination of serogroup W135 and Y specific subclass distribution, an adolescent panel 28 days following a single dose of either tetravalent polysaccharide or conjugate vaccine was used. The sum of the serogroup-specific IgG1 and IgG2 showed strong correlation with the serogroup-specific total IgG determined. The assignment here of IgG1 and IgG2 subclasses to these reference sera will allow more detailed evaluation of meningococcal conjugate and polysaccharide vaccines.
Clinical and Diagnostic Laboratory Immunology
A standardized serum bactericidal assay (SBA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines. We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SBA titers. The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera. The critical assay parameters for the reproducible measurement of SBA titers were found to include the target strain, assay incubation time, and complement. The resulting standardized SBA was used by 10 laboratories to measure functional anticapsular antibody against serogroup A strain F8238 and serogroup C strain C11. In the multilaboratory study, SBA titers were measured in duplicate for 14 pairs of sera (seven adults and seven children) before and after immunization with a quadrivalent polysaccharide (A, C, Y, and W-135) vaccine. The standardized SBA was reliable in all laboratories regardless of experience in performing SBAs. For most sera, intralaboratory reproducibility was ؎1 dilution; interlaboratory reproducibility was ؎2 dilutions. The correlation between median titers (interlaboratory) and enzyme-linked immunosorbent assay total antibody concentrations was high for both serogroup A (r ؍ 0.86; P < 0.001; slope ؍ 0.5) and serogroup C (n ؍ 0.86; P < 0.001; slope ؍ 0.7). The specified assay, which includes the critical parameters of target strain, incubation time, and complement source, will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines.
Neisseria meningitidis serogroup B: laboratory correlates of protection
FEMS Immunology & Medical Microbiology, 2002
Meningococcal disease in the Western countries is frequently caused by Neisseria meningitidis serogroup B. Major efforts have been made to develop a safe and efficacious vaccine against this serogroup which is suitable for use in infants and young children. To assess the quality of the immune response after vaccination with candidate vaccines, laboratory correlates of protection are needed. For serogroups A and C, serum bactericidal activity (SBA) is a well established predictor for protection, but for serogroup B other mechanisms besides SBA may also be involved in conferring protection from disease. Several laboratory methods for identification and evaluation of the immunogenicity of possible vaccine antigens are described in this review.
PloS one, 2010
In 2002 a Meningococcal serogroup C (MenC) conjugate vaccine, with tetanus toxoid as carrier protein, was introduced in the Netherlands as a single-dose at 14 months of age. A catch-up campaign was performed targeting all individuals aged 14 months to 18 years. We determined the MenC-specific immunity before and after introduction of the MenC conjugate (MenCC) vaccine. Two cross-sectional population-based serum banks, collected in 1995/1996 (n = 8539) and in 2006/2007 (n = 6386), were used for this study. The main outcome measurements were the levels of MenC polysaccharide(PS)-specific IgG and serum bactericidal antibodies (SBA) after routine immunization, 4-5 years after catch-up immunization or by natural immunity. There was an increasing persistence of PS-specific IgG and SBA with age in the catch-up immunized cohorts 4-5 years after their MenCC immunization (MenC PS-specific IgG, 0.25 microg/ml (95%CI: 0.19-0.31 microg/ml) at age 6 years, gradually increasing to 2.34 microg/ml,(...
Vaccine, 1999
Vaccination provides a safe and eective means of reducing the risk of laboratory-acquired infection due to some Neisseria meningitidis serogroups. However, there is currently no serogroup B meningococcal vaccine licensed for use in the US. We used an investigational N. meningitidis serogroup B outer membrane vesicle (B:15:P1.7,16) vaccine produced by the National Institute of Public Health (NIPH) in Norway to immunize 20 researchers with occupational risk for disease. Three doses of vaccine were administered via intramuscular injection at 8-week intervals. The vaccine produced moderate or severe pain with 19 (33%) of the 58 doses administered. Reactions were similar following ®rst, second and third doses. The number and severity of reactions peaked at 24 h postvaccination and then gradually waned. Of 16 vaccinees with results available from all blood draws, 12 (75%) showed a fourfold or greater rise in serum bactericidal activity (SBA) against the vaccine type-strain following two doses of vaccine, and 15 (94%) responded after three doses. Geometric mean titers increased by more than sixfold following two doses of vaccine when compared with prevaccination levels, and by more than 11-fold following a third dose. There was no signi®cant dierence between SBA measured using the vaccinee's own complement versus a donor complement source. The NIPH vaccine elicited an excellent bactericidal response against the vaccine type-strain in researchers with an occupational risk for disease. It may be useful for other laboratory personnel who routinely work with meningococcal strains containing similar outer membrane antigens. These ®ndings recon®rm that the NIPH vaccine is immunogenic in adults and support the validity of using properly screened human donor complement in serum bactericidal assays against serogroup B meningococci.
Clinical and diagnostic laboratory immunology, 1997
A standardized serum bactericidal assay (SBA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines. We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SBA titers. The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera. The critical assay parameters for the reproducible measurement of SBA titers were found to include the target strain, assay incubation time, and complement. The resulting standardized SBA was used by 10 laboratories to measure functional anticapsular antibody against serogro...
Vaccine, 2014
The potential protective effect of existing vaccines against serogroup B meningococci, based on outer membrane proteins, is limited by strain restriction and apparent short duration of immune responses. In contrast, meningo-coccal colonization is known to stimulate the production of cross-protective antibodies as defined by the develop-ment of serum bactericidal activity (S BA) against heterologous serogroup B strains. In the current study, a resource of human serum samples and meningococcal carriage strains from studies of longitudinal carriage has been subjected to immunoproteomic analysis to investigate the outer membrane protein antigens associated with the development of S BA to both homologous and heterologous meningococcal serogroup B strains. Proteins from outer membranes of homologous and heterologous strains were separated by two-dimensional electrophoresis and reacted with paired sera which showed an increase in S BA following colonization. Individuals showed differing patterns of reactivity upon colonization, with an increase in S BA being associated with increases in the number of spots detected before and after colonization and/or with increases in the intensity of individual spots. Analysis of immunoreactive spots by mass spectrometry resulted in the identification of 43 proteins potentially associated with the development of S BA against both homologous and heterologous strains. The list of protein immunogens generated included not only well-established antigens but also novel proteins that represent potentially new candidates for inclusion in defined, multicomponent serogroup B vaccines.