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Infection and Immunity, November 2008, p. 5305-5309, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00796-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Serotype-Specific Immune Unresponsiveness to Pneumococcal Conjugate Vaccine following Invasive Pneumococcal Disease{triangledown}

Ray Borrow,1* Elaine Stanford,1 Pauline Waight,2 Matthew Helbert,3 Paul Balmer,1 Rosalind Warrington,1 Mary Slack,4 Robert George,4 and Elizabeth Miller2

Vaccine Evaluation Unit, Health Protection Agency, Manchester Medical Microbiology Partnership, P.O. Box 209, Clinical Sciences Building, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom,1 Immunisation Department, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, United Kingdom,2 Immunology Department, Central Manchester and Manchester Children's NHS Trust, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom,3 Respiratory and Systemic Infection Laboratory, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, United Kingdom4

Received 26 June 2008/ Returned for modification 30 July 2008/ Accepted 2 September 2008

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 ≥0.35 µg/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.

* Corresponding author. Mailing address: Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, P.O. Box 209, Clinical Sciences Building, Manchester Royal Infirmary, Manchester M13 9XZ, United Kingdom. Phone: 44 161 276 6793. Fax: 44 161 276 6792. E-mail: ray.borrow{at}hpa.org.uk

{triangledown} Published ahead of print on 8 September 2008.

Editor: J. N. Weiser

Infection and Immunity, November 2008, p. 5305-5309, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00796-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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