{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T17:04:13Z","timestamp":1758819853744},"reference-count":21,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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 (\u03b1-\u03b4-dex) were lower in PBMCs derived from vaccine failures (<jats:italic>P<\/jats:italic>= 0.044 and<jats:italic>P<\/jats:italic>= 0.029, respectively). There was reduced CD4 cell activation of the patient cells compared to controls following stimulation by CD3 (<jats:italic>P<\/jats:italic>= 0.048). B-cell activation during incubation of PBMCs with the T-cell stimuli, anti-CD3 (<jats:italic>P<\/jats:italic>= 0.044), or anti-CD3 plus anti-CD28 (<jats:italic>P<\/jats:italic>= 0.018) was relatively impaired in patients. Anti-tetanus toxoid IgG concentrations were lower in the vaccine failure group (<jats:italic>P<\/jats:italic>= 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.<\/jats:p>","DOI":"10.1128\/cvi.00481-09","type":"journal-article","created":{"date-parts":[[2010,5,13]],"date-time":"2010-05-13T01:54:11Z","timestamp":1273715651000},"page":"1104-1110","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Functional T-Cell Deficiency in Adolescents Who Experience Serogroup C Meningococcal Disease despite Receiving the Meningococcal Serogroup C Conjugate Vaccine"],"prefix":"10.1128","volume":"17","author":[{"given":"Rachel A.","family":"Foster","sequence":"first","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Carlring","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Lees","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Borrow","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Ramsay","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ed","family":"Kacsmarski","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"McKendrick","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom"},{"name":"Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850"},{"name":"Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom"},{"name":"Immunisation Department, Health Protection Agency Centre for Infections, Colindale, London, United Kingdom"},{"name":"Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew W.","family":"Heath","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Road, Sheffield 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