title: Functional T-cell deficiency in adolescents who experience serogroup C meningococcal disease despite receiving the meningococcal serogroup C conjugate vaccine.
abstract: Some individuals have experienced meningococcal disease despite receiving the meningococcal serogroup C conjugate (MCC) vaccine in adolescence. We sought to determine whether this is due to subclinical functional B- or T-cell immunodeficiency. Of 53 vaccine failures identified by enhanced surveillance of England and Wales from 1999 to 2004, 15 received MCC vaccine in adolescence, 9 of whom were recruited 2 to 6 years following convalescence from meningococcal disease. Their peripheral blood mononuclear cells (PBMCs) were incubated with polyclonal activators designed to mimic T-cell-independent B-cell stimulation by bacterial polysaccharides and the T-cell stimulation provided by the protein component of the conjugate vaccine. Subsequent proliferation and activation of T and B lymphocytes were measured, along with T-cell help to B cells. Compared to age-, sex-, geographically, and ethnicity-matched controls, CD4 T-cell proliferation rates in response to both anti-CD3 (T-cell receptor [TCR]) stimulation and anti-CD3 in the presence of B cells activated through anti-IgD conjugated to dextran (alpha-delta-dex) were lower in PBMCs derived from vaccine failures (P = 0.044 and P = 0.029, respectively). There was reduced CD4 cell activation of the patient cells compared to controls following stimulation by CD3 (P = 0.048). B-cell activation during incubation of PBMCs with the T-cell stimuli, anti-CD3 (P = 0.044), or anti-CD3 plus anti-CD28 (P = 0.018) was relatively impaired in patients. Anti-tetanus toxoid IgG concentrations were lower in the vaccine failure group (P = 0.0385). There was a relative defect of T-cell responsiveness to T-cell-dependent antigen stimulation in MCC vaccine failures, which was manifested in reduced T-cell help to B cells.
authors.affiliation: Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Rd., Sheffield S10 2RX, United Kingdom.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Foster
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carlring
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Mary
authors.initials: M
authors.lastname: Ramsay
authors.forename: Ed
authors.initials: E
authors.lastname: Kacsmarski
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.forename: Michael W
authors.initials: MW
authors.lastname: McKendrick
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Heath
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000276:immunology* / Q000382:microbiology; D022401:Meningococcal Vaccines / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000473:pathology*; D017211:Treatment Failure
chemical_list: D022401:Meningococcal Vaccines; C410218:serogroup C meningococcal conjugate vaccine
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