RT Journal Article
SR Electronic
T1 Functional T-Cell Deficiency in Adolescents Who Experience Serogroup C Meningococcal Disease despite Receiving the Meningococcal Serogroup C Conjugate Vaccine
JF Clinical and Vaccine Immunology
JO Clin Vaccine Immunol
FD American Society for Microbiology
SP 1104
OP 1110
DO 10.1128/CVI.00481-09
VO 17
IS 7
A1 Foster, Rachel A.
A1 Carlring, Jennifer
A1 Lees, Andrew
A1 Borrow, Ray
A1 Ramsay, Mary
A1 Kacsmarski, Ed
A1 Miller, Elizabeth
A1 McKendrick, Michael W.
A1 Heath, Andrew W.
A1 Read, Robert C.
YR 2010
UL http://cvi.asm.org/content/17/7/1104.abstract
AB 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 (α-δ-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.