Safety and immunogenicity of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine administered in a dual-chamber syringe to infants in Belgium and Chile.

To document any unexpected differences in the immune response between study populations and to evaluate immunogenicity and safety of a simplified presentation (dual-chamber syringe) of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine, a multicentre, randomized, comparative study was conducted in Belgium and Chile. A total of 537 healthy infants, 270 in Chile and 267 in Belgium, received PRP-T and DTP vaccines combined in a dual-chamber syringe (D-Ch group, DTP/PRP-T, reconstituted by pressing the plunger of the syringe immediately before injection, n = 239) or combined in a single-chamber syringe (C-In group, DTP@PRP-T, reconstituted immediately before injection, n = 61) or in separate injections (S-In group, DTP + PRP-T, simultaneously injected at separate sites, n = 237) at 3, 4, and 5 months of age. Serum samples were collected before vaccination and at 6 months of age. In the D-Ch group, the incidence of adverse events was comparable to administration of DTP vaccine alone. Higher rates of local and systemic reactions were observed in the Chilean population, possibly due to differences in surveillance practice. The immune response to each vaccine component compared well to that of the separate administration of PRP-T and DTP vaccines, except for higher post-immunization anti-PRP geometric mean titre (GMT) values after separate injections (25.6 micrograms mL-1) than after combined injection with the dual-chamber syringe (17.6 micrograms mL-1) (p = 0.001). An unexpected 'syringe' effect was seen: a greater post-immunization anti-PRP GMT was observed in the D-Ch group (17.6 micrograms mL-1) than in the C-In group (7.7 micrograms mL-1) (p = 0.0001). Whereas pre-immunization GMTs of some antibodies were significantly lower in Chilean than in Belgian infants, the post-immunization GMTs of Chilean infants were two to three times greater for all of the antibodies studied (p < 0.005). Differences in reactogenicity and in the immune response between the study populations or the different vaccine presentations were striking, but are probably of no clinical relevance. The convenient dual-chamber syringe presentation of DTP and PRP-T vaccines is safe and highly immunogenic.

RCT Entities:   Population Interventions Outcomes