Safety and immunogenicity of Biken acellular pertussis vaccine in combination with diphtheria and tetanus toxoid as a fifth dose at four to six yearsof age

Objectives. To evaluate the safety and immunogenicity of Biken acellular pe rtussis vaccine in combination with diphtheria and tetanus toxoid (Biken DT aP) vaccine administered to children 4 to 6 years of age who had previously received four doses of Biken DTaP. Methods. 580 children were enrolled to receive one dose of Biken DTaP. Loca l and systemic reactions were collected by parent diary for all subjects wi thin 3 days after vaccination and in a subset for 14 days. All adverse even ts occurring within 30 days after vaccination were recorded. Results. Any redness and swelling occurred in 59.8 and 61.4%, respectively. Redness or swelling larger than 5 cm/10 cm occurred in 31%/6.1% and 25%/6. 5% of the children, respectively. Any pain was reported in 58.8%, but clini cally significant pain occurred in 2.1% of the children. Fever > 38.0 degre esC occurred in 3.8% of the children. Fussiness, drowsiness, anorexia and v omiting were experienced by 19.7, 15.5, 7.3 and 2.2%, respectively. Sixty-t hree of 247 adverse events (25%) occurring within 30 days after vaccination were assessed to possibly be vaccine-related. Fifty-eight of the 63 possib ly related events (92%) were caused by local reactions as redness, swelling or itchiness. The remaining 5 events included hematoma, headache, stomacha che and sleep disturbance. All local and systemic reactions and adverse eve nts resolved without sequelae. Immunogenicity analysis showed a 4-fold anti body increase to pertussis toxin in 97% of subjects and to filamentous hema gglutinin in 82%. All subjects had postvaccination antibody titers of 0.1 I U/ml or greater against diphtheria and tetanus. Higher prevaccination antib ody titers against diphtheria toxoid, pertussis toxin and filamentous hemag glutinin were associated with a higher frequency of large local reactions. Conclusion. In comparison with a fourth dose of Biken DTaP administered at 18 to 24 months of age in the same population, the rate of local reactions increased after the fifth dose, whereas systemic reactions remained similar ly low or decreased.