Safety and immunogenicity of combined diphtheria-tetanus-pertussis (whole cell and acellular)-Haemophilus influenzae-b conjugate vaccines administered to Indonesian children.

A randomized double-blind trial was conducted to evaluate the safety and immunogenicity of vaccines comprised of diphtheria (D) and tetanus (T) toxoids combined with either a whole cell (P) or an acellular (aP) pertussis component and Haemophilus influenzae type b polyribosylphosphate (PRP) tetanus toxoid conjugate (PRP-T) in Indonesian infants. Three doses of either DTaP, DTaP-PRP-T, or DTP-PRP-T were administered to 930 infants approximately 2-3 months of age and at 2 month intervals thereafter. A booster dose of either DTP-PRP-T or DTaP-PRP-T was administered at 15-18 months of age. Both local and systemic reactions occurred at a significantly (p < 0.001-0.026) higher rate in the group that received whole cell pertussis vaccine versus groups which were immunized with aP containing vaccines. There was no significant difference (p > 0.05) in the rate of adverse events between groups immunized with DTaP or DTaP PRP T. One month after the third dose of vaccine, 99% of subjects had achieved > or =0.1 IU of anti-D and anti-T antibody per ml of serum. The geometric mean titer (GMT) to D was significantly (p < 0.001) higher in the group immunized with DTaP versus the other two groups whereas the anti-T GMT was significantly (p < 0.006) higher for the group immunized with DTP-PRP-T. Both the anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibody levels were significantly (p < 0.001) higher in recipients of acellular versus whole cell pertussis vaccine. In contrast, the anti-B. pertussis agglutinating antibody response was significantly (p < 0.0001) higher in the group immunized with whole cell pertussis vaccine. The anti-PRP GMTs (microg antibody/ml) at 7 months were 0.096, 3.35 and 6.11 for groups immunized with DTaP, DTaP-PRP-T and DTP-PRP-T, respectively. The GMT for those immunized with DTP-PRP-T was significantly (p < 0.001) higher compared to recipients of DTaP-PRP-T. The percent of children who attained > or =0.15 or > or =1 microg/ml after immunization was 18 and 2% for the DTaP group, 93 and 76% for the DTaP-PRP-T group and 97 and 88% for the DTP-PRP-T group. At the > or =1 microg/ml level the difference between the DTaP-PRP0-T and DTP-PRP-T groups was significant (p < 0.01). Children immunized with either DTaP, DTaP-PRP-T, or DTP-PRP-T were reimmunized with DTaP-PRP-T whereas a portion of children immunized with DTP PRP T where also boosted with this vaccine at 15-18 months of age. There was a vigorous anamnestic response to the D and T components with all children possessing > or =0.1 IU/ml. There was also a substantial increase in anti-PT, anti-FHA and B. pertussis agglutinating antibodies. The poorest anti-PT response was seen among children receiving DTP-PRP-T for both primary and reimmunization while the highest agglutinating antibody response followed receipt of 4 doses of DTP-PRP-T. Greater than 80% of children immunized with either DTP PRP T or DTaP-PRP-T possessed > or =0.15 microg/ml before boosting versus 38% for those vaccinated with DTaP (p < 0.001). Primary immunization with DTP-PRP-T resulted in a significantly (p < 0.05) higher percentage (72%) maintaining > or =1 microg/ml compared to those immunized with DTaP-PRP-T (46%). Prior to reimmunization, the anti-PRP GMT was significantly (p < 0.005) higher for children immunized with 3 doses of DTP-PRP-T versus DTaP-PRP-T. Subsequent to reimmunization, > or =95% of subjects attained > or =1 microg/ml.