Serotype-specific immune unresponsiveness to pneumococcal conjugate vaccine following invasive pneumococcal disease.
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.
Borrow
Ray
R
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
Stanford
Elaine
E
Waight
Pauline
P
Helbert
Matthew
M
Balmer
Paul
P
Warrington
Rosalind
R
Slack
Mary
M
George
Robert
R
Miller
Elizabeth
E
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
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C053135:pneumococcal polysaccharide, type 7
Vaccine. 2007 Jan 4;25(2):306-13
16914241
Curr Opin Pediatr. 1998 Apr;10(2):208-15
9608902
J Immunol. 2005 Sep 1;175(5):3084-91
16116197
Lancet Infect Dis. 2007 Sep;7(9):597-606
17714673
Pediatr Infect Dis J. 1999 Oct;18(10 Suppl):S17-22
10530569
Lancet. 1985 Aug 31;2(8453):468-71
2863493
Am J Dis Child. 1986 Feb;140(2):135-8
3946323
Pediatr Infect Dis J. 2007 Aug;26(8):716-22
17848884
J Investig Med. 1997 Feb;45(2):57-68
9084576
Annu Rev Immunol. 1995;13:655-92
7612238
J Infect Dis. 1975 Jul;132(1):69-74
1080178
J Immunol. 2004 Jan 1;172(1):532-9
14688364
JAMA. 1977 Dec 12;238(24):2613-6
21973
J Infect Dis. 2003 May 15;187(10):1629-38
12721943
Lancet. 1999 Aug 14;354(9178):590-2
10470718
Pediatr Infect Dis. 1986 Jan-Feb;5(1):39-44
3945574
J Immunol Methods. 2005 Jan;296(1-2):135-47
15680158
Pediatr Infect Dis J. 2006 Apr;25(4):312-9
16567982
Vaccine. 2007 Mar 22;25(13):2445-50
17052816
J Infect. 2007 Oct;55(4):300-9
17692384
Clin Infect Dis. 2002 Apr 1;34(7):1025-8
11880971
Vaccine. 2000 Dec 8;19(9-10):1159-66
11137252
J Infect Dis. 1983 Jul;148(1):131-7
6886479
Antonie Van Leeuwenhoek. 1990 Jun;58(1):1-47
2195989
J Pediatr. 1996 Dec;129(6):828-35
8969724
Vaccine. 2007 Aug 21;25(34):6321-5
17629373