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Infection and Immunity, December 2005, p. 8130-8135, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8130-8135.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Th2-Associated Local Reactions to the Acellular Diphtheria-Tetanus-Pertussis Vaccine in 4- to 6-Year-Old Children

Julie Rowe,1 Stephanie T. Yerkovich,1 Peter Richmond,2 Devinda Suriyaarachchi,1 Elizabeth Fisher,3 Leonie Feddema,3 Richard Loh,3 Peter D. Sly,1 and Patrick G. Holt1*

Telethon Institute for Child Health Research and Centre for Child Health Research, Faculty of Medicine and Dentistry, The University of Western Australia, Perth, Western Australia, Australia,1 Department of Paediatrics, The University of Western Australia, Perth, Western Australia, Australia,2 Department of Clinical Immunology, Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia3

Received 20 June 2005/ Returned for modification 25 July 2005/ Accepted 12 September 2005

Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis) (DTaP) are being progressively introduced into vaccination programs worldwide, with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP) vaccine. The DTaP vaccine has an improved safety profile in infants, but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses. We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP (n = 30) or DTwP (n = 16) and by correlating these parameters, in particular cytokine responses, with expression of local side effects at the injection site. Large local reactions (≥50-mm diameter) 24 to 72 h after receiving the DTaP booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically "high Th2 responders" as detected by in vitro responsiveness to polyclonal mitogen. Our findings suggest that priming during infancy with DTaP promotes stable, boostable Th2-polarized immunity against vaccine antigens, which in a significant subset of children is subsequently associated with local reactions at the booster site. The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory.

* Corresponding author. Mailing address: Division of Cell Biology, Telethon Institute for Child Health Research, P.O. Box 855, West Perth WA 6872, Australia. Phone: 61 8 9489 7838. Fax: 61 8 9489 7707. E-mail: patrick{at}ichr.uwa.edu.au.

Editor: D. L. Burns

Infection and Immunity, December 2005, p. 8130-8135, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8130-8135.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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