title: Serotype-specific immune unresponsiveness to pneumococcal conjugate vaccine following invasive pneumococcal disease.
abstract: Following the introduction of the pneumococcal 7-valent conjugate vaccine (PCV7) into the routine infant immunization schedule in England, Wales, and Northern Ireland, pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered as a clinical service to all children within the program with invasive pneumococcal disease (IPD) to confirm an adequate antibody response to PCV7. As of March 2008, serum samples taken within 14 to 90 days of vaccination had been submitted from 107 children who had received one or more doses in the second year of life. Sera were assayed by a multiplexed microsphere assay incorporating both cell wall polysaccharide and serotype 22F adsorption. A protective serotype-specific antibody level was defined as a concentration of > or = 0.35 microg/ml. Eight children failed to develop a response to their infecting serotype (6B [n = 4], 18C [n = 2], 4 [n = 1], and 14 [n = 1]), despite receiving at least three doses of PCV7 in the second year of life or two doses in the second and two or three in the first year of life. A further two children were nonresponsive to a serotype (6B) different than that causing disease. None of the 10 children had a clinical risk factor for IPD. Two had marginally low levels of total serum IgG but mounted adequate responses to the other six PCV serotypes. This serotype-specific unresponsiveness may reflect immune paralysis due to large pneumococcal polysaccharide antigen loads and/or a potential genetic basis for nonresponse to individual pneumococcal serotypes.
authors.affiliation: Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester M13 9XZ, United Kingdom. ray.borrow@hpa.org.uk
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Elaine
authors.initials: E
authors.lastname: Stanford
authors.forename: Pauline
authors.initials: P
authors.lastname: Waight
authors.forename: Matthew
authors.initials: M
authors.lastname: Helbert
authors.forename: Paul
authors.initials: P
authors.lastname: Balmer
authors.forename: Rosalind
authors.initials: R
authors.lastname: Warrington
authors.forename: Mary
authors.initials: M
authors.lastname: Slack
authors.forename: Robert
authors.initials: R
authors.lastname: George
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012703:Serotyping
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C053135:pneumococcal polysaccharide, type 7
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