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

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 werefilamentous 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.