Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toroid conjugate (PRP-T) and diphtheria-te tanus-acellular (two component) pertussis (DTaP) combination vaccine, a ran domized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in T urkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediat ely prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) receive d DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule gr oup (As-S). The third group (N = 137) also received DTaP + PRP-T at separat e sites, but at 2, 4 and 6 months, and are referred to as the associated, l ong schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S a nd As-S) received, at the age of 12-14 months, a booster dose of DTaP vacci ne associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. T he immune response to Hib capsular polysaccharide, however, was significant ly lower after combined administration (Co-S group) than after associated ( As-S group) administration (P < 0.0001), with a similar trend among both co untries (GMTs, 1.78 mu g/ml and 6.19 mu g/ml in Belgium, and 5.02 mu g/ml a nd 11.67 mu g/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than T urkish infants (P less than or equal to 0.001 for all antigens), with a sim ilar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population , possibly due to differences in reporting practice. Our results indicate ( 1) that the combination vaccine, DTaP//PRP-T, represents an important impro vement over the existing uncombined vaccines; (2) that immunogenicity studi es should include at least one booster injection to evaluate priming effect s by combined vaccines; and (3) that it is feasible and valuable to co-rand omize combination vaccine studies in sufficiently different geographical ar eas and child populations. (C) 1999 Elsevier Science Ltd. All rights reserv ed.