An Evaluation of the Safety and Immunogenicity of a Five-Component Acellular Pertussis, Diphtheria, and Tetanus Toxoid Vaccine (Dtap) When Combined with a Haemophilus Influenzae Type B-Tetanus Toxoid

Abstract

Objective. Immunologic interference particular to the Haemophilus influenzae type b (Hib) response has been observed with previous acellular pertussis-Hib combination vaccines. To test this hypothesis a clinical trial to assess the safety and immunogenicity of a five-component ( pertussis toroid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) when given simultaneously with a lyophilized Hib-tetanus toroid conjugate vaccine (PRP-T) in infants at 2, 4, 6, and 18 months of age was conducted. The study compared two methods of administration: both vaccines combined in a single syringe and administered as a single injection, or both vaccines administered concurrently but at separate sites of injection.Methods. Healthy 2-month- old infants were enrolled at the National Taiwan University Hospital. DTaP , PRP-T, and oral poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction information was collected by telephone 2 days after each vaccination. Serum was collected at 2, 6, 7, 18, and 19 months of age .Results. One hundred thirty-five healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18-month booster: 68 received the combined vaccine and 67 the separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were reported. Serologic responses were comparable between the groups. Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7 months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN (100 vs 77) , and FIM (922 vs 702). At 19 months, pertussis results were , for combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197), and FIM (892 vs 732). Only the 7- month PT response in the combined group was significantly higher (combined 131 EU/ mL vs separate 105 EU/mL). After the third dose (age 6 months), all subjects achieved serologic serum antibody levels indicative of protection against Hib, diphtheria, tetanus, and poliovirus types 1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of protection ( greater than or equal to 0.15 mu g/mL) against Hib after only two doses. At 7 months, anti-PRP geometric mean titer values were 11.8 mu g/mL in the combined group compared with 13.0 mu g/mL in the separate group. The anti - PRP geometric mean titers after the 18-month booster were 58 .5 mu g/mL in the combined group versus 55.3 mu g/mL in the separate group.Conclusion . The five-component DTaP vaccine may be combined with PRP-T vaccine without clinically significant immunologic interaction when given in a 2; 4-, 6 -, and 18-month schedule.