The eect of reconstitution of an Haemophilus in¯uenzae type b-tetanus toxoid conjugate (PRP-T) vaccine on the immune responses to a diphtheria±tetanus-whole cell pertussis (DTwP) vaccine: a ®ve-year follow-up K. Hoppenbrouwers a, *, M. Roelants a , C. Ethevenaux b , C. Vandermeulen a , J. Knops a , J. Desmyter c a Department of Youth Health Care, Katholieke Universiteit Leuven, Kapucijnenvoer 35, 3000 Leuven, Belgium b Pasteur Me Ârieux Connaught, Lyon, France c Rega Institute and University Hospitals, Leuven, Belgium Received 10 August 1998; received in revised form 18 January 1999; accepted 28 January 1999 Abstract Controversial results have been obtained from previous studies on the combined administration of Haemophilus in¯uenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria±tetanus-whole-cell pertussis (DTwP) combination vaccines, with regard to possible reciprocal interference between the constituent antigens. To document the priming eect and possible long-term immunogenic interference of PRP-T and DTwP combination vaccines, a randomized, double-blind, controlled study was conducted in Belgium. A total of 168 healthy infants received, at 3, 4 and 5 months of age, DTwP vaccine mixed just prior to injection either with PRP-T vaccine (group A, DTwP//PRP-T, N=85) or with placebo (group B, DTwP//Placebo, N=83). At the age of 14 months, children of both groups were randomized to receive either a dose of DTwP//PRP-T vaccine (subgroups A1 and B1) or a dose of Hib polysaccharide (PRP) vaccine (subgroups A2 and B2). Those children in subgroups A1 and B1 had an additional serum sample taken at the age of 5 years (at the time of a DT booster). The immune response to Hib polysaccharide at the age of 4, 5 and 6 months con®rmed the excellent immunogenicity pro®le of PRP-T in infants. In addition, the vigorous anamnestic response (i.e. a 20-fold increase of GMT) to a booster dose of the plain capsular polysaccharide (PRP) re¯ected the ecient Hib-priming induced by the combined DTwP//PRP-T vaccine. Reconstitution of PRP-T with DTwP did not aect the immune response to diphtheria toxoid or pertussis agglutinins. Nevertheless, at almost any time point during the ®ve-year follow-up, the tetanus antitoxin GMT values were signi®cantly lower in the DTwP//PRP-T group (A and A1) than in the DTwP//Placebo group (B and B1). Despite the suppressive eect on GMT values, intergroup dierences in rates of seroprotection were never signi®cant, except after doses 2 and 3 for which there were lower percentages of children in group A with antitoxin titers >0.05 IU/mL and >1.0 IU/mL. In the group primed with the combined DTwP//PRP-T vaccine, (1) a DT booster dose at the age of 5 years provoked a 150-fold increase in tetanus antitoxin GMT, (2) a high tetanus antitoxin GMT value was attained (GMT=19.3 IU/mL) and (3) all children in this group had tetanus antitoxin titers >1.0 IU/mL, so it may be concluded that all these children will still be protected against tetanus until at least the age of the next recommended booster dose (i.e. the age of 15 years). No dierences in the occurrence of adverse events were observed between the groups who received the DTwP//PRP-T vaccine or the DTwP//Placebo vaccine, both vaccines being associated with events customarily attributable to DTwP (data not shown). Our results indicate (1) that the combination vaccine, DTwP//PRP-T, represents a safe and eective alternative for the Vaccine 17 (1999) 2588±2598 0264-410X/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S0264-410X(99)00047-X * Corresponding author. Tel.: +32-16-336-873; fax: +32-16-336-883. E-mail address: karel.hoppenbrouwers@med.kuleuven.ac.be (K. Hoppenbrouwers)