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Cellular Immunity as a Potential Cause of Local Reactions to Booster Vaccination With Diphtheria and Tetanus Toxoids and Acellular Pertussis Antigens

Scheifele, David W. MD*; Ochnio, Jan J. MD, PhD*; Halperin, Scott A. MD

The Pediatric Infectious Disease Journal: November 2009 - Volume 28 - Issue 11 - p 985-989
doi: 10.1097/INF.0b013e3181a9cc2a
Original Studies

Background: Booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines restore waning serum antibody values but frequently cause local inflammation. Cell-mediated immunity (CMI) develops after primary DTaP vaccination and might contribute to local reactions to booster doses, a possibility explored in this study.

Methods: Healthy 4 to 5-year-old children were bled before DTaP.IPV booster vaccination. Peripheral blood mononuclear cells were tested for proliferative responses to D toxoid (DT), T toxoid, pertussis toxoid, pertactin, filamentous hemagglutinin and fimbriae (FIM) types 2, 3, and cytokine release patterns assessed. Proliferative responses were examined in relation to prebooster serum antibody concentrations and local reaction rates, previously reported.

Results: Among 167 subjects tested, proliferative response rates were: filamentous hemagglutinin 95%, pertussis toxoid 90%, T toxoid 84%, pertactin 67%, DT 41%, and FIM 31%. Responses were present to 3 to 6 antigens in 87% of subjects and absent altogether in 2%. Subjects without residual pertussis antibodies often had CMI to pertussis antigens. Subjects with CMI had higher corresponding serum antibody concentrations before the booster, compared with CMI-negative subjects. CMI responses were mixed TH1/TH2 type by cytokine profile for all antigens. Injection site erythema (≥5 mm) was twice as frequent in those with than without CMI to DT (P = 0.009) or FIM (P = 0.042, Fisher exact test), the only antigens evaluable.

Conclusion: CMI to vaccine antigens was often detectable in children before preschool booster vaccination and preliminary evidence suggests a role for CMI in local reactions to this dose.

From the *Vaccine Evaluation Center, University of British Columbia, Vancouver, British Columbia, Canada; and the †Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia, Canada.

Accepted for publication April 13, 2009.

Supported by funds from a grant in aid of research from Sanofi Pasteur, Swiftwater, PA. The original study was funded by the Canadian Institutes for Health Research. Jenny Wang and Shuyu Fan provided excellent technical assistance and statistical support, respectively.

Study results presented in part at the 10th Annual Conference on Vaccine Research, Baltimore, MD, April 30–May 2, 2007 (abstract S05).

Address for correspondence: David Scheifele, Vaccine Evaluation Center, BC Children's Hospital (Rm L427), 4500 Oak Street, Vancouver, British Columbia, Canada V6H 3N1. E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.