Randomized Clinical Trial To Evaluate the Immunogenicity of Quadrivalent Meningococcal Conjugate and Polysaccharide Vaccines in Adults in the United Kingdom

Ramasamy, Maheshi; Clutterbuck, Elizabeth A.; Haworth, Kim E.; Bowman, Jaclyn; Omar, Omar; Thompson, Amber; Blanchard-Rohner, Géraldine; Yu, Ly-Mee; Snape, Matthew D.; Pollard, Andrew J.

doi:10.1128/cvi.00099-14

Cited by 13 publications

(9 citation statements)

References 21 publications

(23 reference statements)

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“…In this study we observed similar MenA- and MenC-specific SBA titres following a single dose of both MenACWY-PS and MenACWY-CRM, which is consistent with previous immunogenicity data in adults [ 46 , 47 ]. No further rise in SBA titres was seen following the additional dose of vaccine; this is not surprising as polysaccharide vaccines do not induce immunology memory, and a minimal interval of ~4 months is required for effective booster responses [ 48 ].…”

Section: Discussionsupporting

confidence: 92%

High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

et al. 2017

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Background Neisseria meningitidis is a globally important cause of meningitis and septicaemia. Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. Here we apply contemporary methods to describe B-cell responses to meningococcal polysaccharide and conjugate vaccines.MethodsTwenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination and 7, 21 and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray.ResultsSeven days after an initial dose of either vaccine, a gene expression signature characteristic of plasmablasts was detectable. The frequency of newly generated plasma cells (CXCR3+HLA-DR+) and the expression of transcripts derived from IGKC and IGHG2 correlated with immunogenicity. Notably, using an independent dataset, the expression of glucosamine (N-acetyl)-6-sulfatase was found to reproducibly correlate with the magnitude of immune response. Transcriptomic and flow cytometric data revealed depletion of switched memory B cells following plain-polysaccharide vaccine.ConclusionsThese data describe distinct gene signatures associated with the production of high-avidity antibody and a plain-polysaccharide-specific signature, possibly linked to polysaccharide-induced hyporesponsiveness.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0400-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

et al. 2017

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“…We isolated naive, MZ, IgM memory and IgG memory baseline B‐cell subsets, in addition to PCs 7 days after each vaccination (). This time point was chosen as previous work from our laboratory using the same vaccine regime has shown the presence of significant numbers of antigen‐specific PCs 7 days after both vaccine doses, 14 and induction of effective antibody responses in both groups 15 . Hence, sorting PCs at this time point would capture a population enriched for vaccine antigen specificity.…”

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confidence: 99%

“…This time point was chosen as previous work from our laboratory using the same vaccine regime has shown the presence of significant numbers of antigen-specific PCs 7 days after both vaccine doses, 14 and induction of effective antibody responses in both groups. 15 Hence, sorting PCs at this time point would capture a population enriched for vaccine antigen specificity. We further sorted day 7 PCs based on human leukocyte antigen (HLA)-DR expression, to distinguish recently activated PCs (HLA-DR + ) likely to be enriched for vaccine specificity, from long-lived PCs (HLA-DR -), which are considered to be displaced from the bone marrow by arrival of the newly generated PCs and likely have a broader range of specificities.…”

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confidence: 99%

BCR repertoire sequencing: different patterns of B‐cell activation after two Meningococcal vaccines

et al. 2015

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Next-generation sequencing was used to investigate the B cell receptor heavy chain transcript repertoire of different B cell subsets (naïve, marginal zone, IgM memory and IgG memory) at baseline, and of plasma cells 7 days following administration of serogroup ACWY meningococcal polysaccharide and protein-polysaccharide conjugate vaccines. Baseline B cell subsets could be distinguished from each other using a small number of repertoire properties (clonality, mutation from germ-line and complementarity-determining region 3 length) that were conserved between individuals. However, analyzing the complementarity-determining region 3 amino acid sequence (which is particularly important for antigen binding) of the baseline subsets showed few sequences shared between individuals. In contrast, day 7 plasma cells demonstrated nearly tenfold greater sequence sharing between individuals than the baseline subsets, consistent with the plasma cells being induced by the vaccine antigen, and sharing specificity for a more limited range of epitopes. By annotating plasma cell sequences based on IgG subclass usage and mutation, and also comparing them to the sequences of the baseline cell subsets, we were able to identify different signatures after the polysaccharide and conjugate vaccines. Plasma cells produced after conjugate vaccination were predominantly IgG1, and most related to IgG memory cells. In contrast, after polysaccharide vaccination, the plasma cells were predominantly IgG2, less mutated, and were equally likely to be related to marginal zone, IgM memory or IgG memory cells. High-throughput B cell repertoire sequencing thus provides a unique insight into patterns of B cell activation not possible from more conventional measures of immunogenicity.

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“…Lalwani et al [60] assessed the immunogenicity of a meningococcal ACWY-CRM conjugate vaccine in healthy Indian subjects aged 2 to 75 years and concluded that it generated a robust immune response; however, the aged subjects were included in a group of people aged 19–75 years, and so it was difficult to distinguish the specific response of the subjects older than 60 years in this study. The same occurred in the study of Ramasamy et al [61], which compared the immunogenicity of a quadrivalent conjugate vaccine (MenACWY-CRM) with that of a quadrivalent polysaccharide vaccine (MenACWY-PS) in healthy adults aged 18–70 years; both vaccines were considered immunogenic, but again the older individuals were not evaluated separately.…”

Section: Meningococcal Vaccinesmentioning

confidence: 90%

Study of the Immune Response in the Elderly: Is It Necessary to Develop a Vaccine againstNeisseria meningitidisfor the Aged?

Lima

Gaspari

2019

Journal of Aging Research

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Literature reports the association between aging and decline in the immune system function. The elderly have a higher risk of developing infectious diseases and are often less responsive to vaccines that are effective in the young. The case fatality rate of invasive meningococcal disease is higher in the elderly; therefore, vaccination for this population should be evaluated. Although new vaccines have been developed against Neisseria meningitidis, there is still a need to evaluate a vaccine for those older than 60 years, as the currently licensed vaccines are not indicated for this population.

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Randomized Clinical Trial To Evaluate the Immunogenicity of Quadrivalent Meningococcal Conjugate and Polysaccharide Vaccines in Adults in the United Kingdom

Cited by 13 publications

References 21 publications

High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

BCR repertoire sequencing: different patterns of B‐cell activation after two Meningococcal vaccines

Study of the Immune Response in the Elderly: Is It Necessary to Develop a Vaccine againstNeisseria meningitidisfor the Aged?

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