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Journal ArticleDOI

Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group.

TLDR
The standardized SBA was reliable in all laboratories regardless of experience in performing SBAs, and will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines.
Abstract
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 strains 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.

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Molecular signatures of antibody responses derived from a systems biology study of five human vaccines

TL;DR: A large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses.
Journal ArticleDOI

Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: reevaluation of correlates of protection.

TL;DR: The results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.
Journal ArticleDOI

Validation of Serological Correlate of Protection for Meningococcal C Conjugate Vaccine by Using Efficacy Estimates from Postlicensure Surveillance in England

TL;DR: Age-specific efficacy estimates for MCC vaccines obtained from postlicensure surveillance in England were compared with the efficacy predicted by the percentage of individuals in these age groups with rSBA titers above different cutoffs, suggesting that continuing protection is less dependent on the SBA level at the time of exposure but is more reliant on immunologic memory.
Journal ArticleDOI

Impact of meningococcal C conjugate vaccine in the UK

TL;DR: There is some evidence of herd immunity in unvaccinated cohorts of the target age groups, ranging from a reduction in disease incidence of 34% in 9-14 year olds to 61% in 15-17 year olds, and surveillance of the genotypic and phenotypic characteristics of invasive and carriage isolates has shown no evidence to date of capsular switching from serogroups C to serogroup B.
References
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Journal ArticleDOI

Human immunity to the meningococcus i. the role of humoral antibodies

TL;DR: It was found that the proportion of individuals with serum bactericidal activity to meningococci of serogroups A, B, and C was reciprocally related to the incidence of disease, and susceptible persons are deficient in antimeningococcal antibodies because they have not received significant exposure to mena antigens in the past.
Journal ArticleDOI

Human immunity to the meningococcus iv. immunogenicity of group a and group c meningococcal polysaccharides in human volunteers

TL;DR: The high molecular weight group A and group C meningococcal polysaccharides were excellent immunogens in six human volunteers and were highly meningococcocidal in the presence of complement.
Journal ArticleDOI

Human immunity to the meningococcus : iii. preparation and immunochemical properties of the group a, group b, and group c meningococcal polysaccharides

TL;DR: A passive hemagglutination test developed to measure antibodies to the polysaccharides demonstrated the specificity of these antigens, and this test could be used for serogrouping meningococcal isolates.
Journal ArticleDOI

Clinical Efficacy of Meningococcus Group A Capsular Polysaccharide Vaccine in Children Three Months to Five Years of Age

TL;DR: Meningococcal Group A vaccine appears efficacious in young infants and children, although five to seven cases of meningitis or sepsis would have been expected within the year.
Journal ArticleDOI

Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide a vaccine

TL;DR: Overall, vaccine efficacy declined from 87% 1 year after vaccination to 70% and 54% at 2 and 3 years, respectively, and a single dose of group A meningococcal vaccine does not yield lasting clinical protection in children less than 4 years of age.
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