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

Abstract

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.

Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine

“…Consistent with previous reports, we observed the upregulation of genes associated with terminally differentiated, antibody‐secreting B cells (plasma cells) at 7 days post‐vaccination (Obermoser et al , 2013; O'Connor et al , 2017). Of note, we identified a particular gene encoding an immunoglobulin light chain molecule, IGLV9‐49, that was upregulated after vaccination with 4CMenB vaccine compared with control vaccines alone.…”

“…Finally, we defined baseline whole blood gene signatures that were predictive of vaccine immunogenicity and reactogenicity. There are an increasing number of studies describing transcriptional responses to immunisation in adults (Obermoser et al, 2013;Nakaya et al, 2015;O'Connor et al, 2017). However, there are few data describing transcriptional regulation following infant immunisation-despite most vaccination programmes being targeted to this population (ECDC, 2020; WHO, 2018).…”

Innate immune signatures to a partially-efficacious HIV vaccine predict correlates of HIV-1 infection risk

“…In our pre-specified analysis plan, gene expression correlations were restricted to the clusters discovered by GSEA and not the data-driven clusters identified and display in the UMAPs ( Fig 2B–2D ), in order to limit the number of comparisons and thereby reduce the likelihood of false discoveries. However, because other groups have identified plasmablast signatures that are associated with subsequent antibody titers after meningococcal [ 45 ], yellow fever [ 46 ], malaria [ 47 ], and influenza [ 48 ] vaccination, we note here that the genes we identified in cluster IV represent a plasmablast signature ( S3 Table ). Consistent with these other studies, a further exploratory analysis indicates that the increase in expression of genes in cluster IV on Day 7 was positively correlated with 92TH023 gp120 (AE) specific IgG measured at Month 6.5 (rho = 0.48, p = 0.02) and Month 12 (rho = 0.66, p = 0.0009).…”

Glycoconjugate vaccines: some observations on carrier and production methods

“…However, the mechanism by which the response to serotype W is reduced in the pure polysaccharide vaccine is unclear, although it is suggested that there may be some sort of negative feedback mechanism present when polysaccharide vaccines are used. This may be explained by O'Connor et al (2017), who found that as well as being less effective at eliciting a response, polysaccharide vaccines might take a role in actively depleting B memory cells when used as a booster vaccine, a mechanism that may also explain the findings of Rothstein et al (1991). Borja-Tabora et al (2015) and Holme et al (2015) studied a meningococcal vaccine (Men) with the serotypes A, C, W and Y polysaccharides either linked to TT as a glycoconjugate or as a polysaccharide-only vaccine.…”