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 i mmunogenicity of vaccines comprised of diphtheria to) and tetanus (T) toxoi ds combined with either a whole cell (P) or an acellular (aP) pertussis com ponent and Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toroid 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 eit her DTP-PRP-T or DTaP-PRP-T was administered at 15-18 months of age, Both l ocal and systemic reactions occurred at a significantly (p less-than 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 n o significant difference (p greater-than 0.05) in the rate of adverse event s between groups immunized with DTaP or DTaP-PRP-T. One month after the thi rd dose of vaccine, 99% of subjects had achieved greater than or equal to 0 .1 IU of anti-D and anti-T antibody per ml of serum. The geometric mean tit er (GMT) to D was significantly ( p less-than 0.001) higher in the group im munized with DTaP versus the other two groups whereas the anti-T GMT was si gnificantly( p less-than 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 less-than 0.001) higher in recip ients of acellular versus whole cell pertussis vaccine. In contrast, the an ti-B. pertussis agglutinating antibody response was significantly(p less-th an 0.0001) higher in the group immunized with whole cell pertussis vaccine. The anti-PRP GMTs (mu g 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. Th e GMT for those immunized with DTP PRP-T was significantly (p less-than 0.0 01) higher compared to recipients of DTaP-PRP-T. The percent of children wh o attained greater than or equal to 0.15 or greater than or equal to 1 mu g /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 greater th an or equal to 1 mu g/ml level the difference between the DTaP-PRP-T and DT P-PRP-T groups was significant (p less-than 0.01). Children immunized with either DTaP, DTaP-PRP-T. or DTP-PRP-T were reimmunized with DTaP-PRP-T wher eas 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 greater than or equal to 0.1 IU/ml. There was also a s ubstantial increase in anti-PT, anti-FHA and B, pertussis agglutinating ant ibodies. 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 dr DTaP-PRP-T possessed great er than or equal to 0.15 mu g/ml before boosting versus 38% for those vacci nated with DTaP (p less-than 0.001). Primary immunization with DTP-PRP-T re sulted in a significantly (p less-than 0.05) higher percentage (72%) mainta ining greater than or equal to 1 mu g/ml compared to those immunized with D TaP PRP-T (46%). Prior to reimmunization, the anti-PRP GMT was significantl y (p less-than 0.005) higher for children immunized with 3 doses of DTP-PRP -T versus DTaP-PRP-T Subsequent to reimmunization. greater than or equal to 95% of subjects attained greater than or equal to 1 mu g/ml. (C) 1999 Else vier Science Ltd. All rights reserved.