Safety and immunogenicity of six acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fifth dose in four- to six-year-old children

Objective. To evaluate the safety and immunogenicity of 6 different acellul ar pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) a nd with 1 licensed whole-cell pertussis vaccine (DTwP) as a fifth dose in c hildren who had previously received the same DTaP, a different DTaP, or DTw P as primary and fourth-dose vaccinations. Methods. Healthy 4- to 6-year-old children were enrolled at 5 National Inst itute of Allergy and Infectious Diseases Vaccine Treatment and Evaluation U nits to receive a fifth dose of a DTaP or DTwP vaccine. All had been random ly assigned to receive 3 primary doses of DTaP or DTwP at 2, 4, and 6 month s and a fourth-dose booster at 15 to 20 months of age as part of earlier Na tional Institutes of Health multicenter acellular pertussis vaccine trials. Parents recorded the occurrence and magnitude of fever, irritability, and injection site redness, swelling, and pain for 3 days after vaccination. Se ra obtained before and 1 month after the booster vaccination were analyzed by enzyme-linked immunosorbent assay for antibody to pertussis toxin, filam entous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxoi d. Safety and/or immunogenicity data are reported for 317 children who rece ived DTaP and 10 children who received DTwP. Results. Fever and moderate or severe irritability were uncommon following the fifth dose of DTaP vaccine and were generally less frequent than follow ing the fourth dose. However, for the DTaP vaccine groups, redness, swellin g, and pain increased in prevalence compared with the fourth dose. The time course and frequency of reactions following DTaP vaccination were generall y similar in children who received the same DTaP, a different DTaP, or DTwP for previous doses in the 5- dose series. No significant differences among the DTaP vaccines were detected in the occurrence of reactions, but the st atistical power to detect differences was limited by sample size. Significant increases in antibodies directed against the included antigens were observed for all DTaP vaccines in paired pre- and post-fifth dose sera . Post-fifth dose antibody concentrations differed significantly among the DTaP vaccines. Some children in the study showed an antibody response to an antigen not reported to be in the DTaP vaccine. Conclusion. All the studied DTaP vaccines performed similarly with regard t o reactions, whether given as a fifth sequential dose of the same vaccine, a mix of different DTaP vaccines in the 5-dose sequence, or after 3 DTwP an d 1 DTaP vaccinations. Large injection site reactions occurred more frequen tly after the fifth dose of DTaP than after the previous 4 doses. A fifth d ose of all DTaP vaccines induced an antibody response to those antigens con tained in the vaccine. No DTaP was consistently most or least reactogenic o r immunogenic.