title: High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine.
abstract: 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.
  
  
  
  Twenty 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.
  
  
  
  Seven 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.
  
  
  
  These 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.
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK. daniel.oconnor@paediatrics.ox.ac.uk.|NIHR Oxford Biomedical Research Centre, Oxford, UK. daniel.oconnor@paediatrics.ox.ac.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Connor
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Clutterbuck
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Snape
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Maheshi N
authors.initials: MN
authors.lastname: Ramasamy
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Dominic F
authors.initials: DF
authors.lastname: Kelly
authors.affiliation: Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Churchill Hospital, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D022401:Meningococcal Vaccines / Q000276:immunology*; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000276:immunology*; D011897:Random Allocation; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate