Functional T-cell deficiency in adolescents who experience serogroup C meningococcal disease despite receiving the meningococcal serogroup C conjugate vaccine.
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.
Foster
Rachel A
RA
Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Rd., Sheffield S10 2RX, United Kingdom.
Carlring
Jennifer
J
Lees
Andrew
A
Borrow
Ray
R
Ramsay
Mary
M
Kacsmarski
Ed
E
Miller
Elizabeth
E
McKendrick
Michael W
MW
Heath
Andrew W
AW
Read
Robert C
RC
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
D022401:Meningococcal Vaccines; C410218:serogroup C meningococcal conjugate vaccine
Epidemiol Infect. 1987 Dec;99(3):591-601
3123263
Clin Diagn Lab Immunol. 2004 Mar;11(2):272-9
15013975
J Immunol Methods. 2005 Jan;296(1-2):135-47
15680158
J Infect Dis. 2006 Dec 15;194(12):1745-52
17109348
Vaccine. 2005 Mar 18;23(17-18):2222-7
15755600
Clin Infect Dis. 2008 Jan 15;46(2):186-92
18171249
Clin Exp Immunol. 2000 Jan;119(1):1-3
10671089
FEMS Microbiol Rev. 2007 Jan;31(1):101-7
17168998
Infect Immun. 2002 Mar;70(3):1301-9
11854214
J Immunol. 2004 Jan 1;172(1):532-9
14688364
Clin Diagn Lab Immunol. 2002 Jul;9(4):872-6
12093688
J Immunol. 2008 Feb 15;180(4):2165-73
18250423
Clin Vaccine Immunol. 2009 May;16(5):692-8
19279166
J Med Microbiol. 2002 Sep;51(9):717-722
12358061
J Immunol. 1991 Feb 1;146(3):833-9
1703179
J Infect Dis. 2008 Mar 1;197(5):737-43
18271745
Clin Diagn Lab Immunol. 1997 Mar;4(2):156-67
9067649
Clin Infect Dis. 2002 Jan 15;34(2):191-7
11740707
J Immunol. 2008 Dec 15;181(12):8258-66
19050242
Lancet. 2004 Jul 24-30;364(9431):365-7
15276396