Objective: To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic.
Design: Randomized clinical trial.
Setting: Suburban New Orleans pediatric population.
Participants: Convenience sample of 150 healthy infants.
Methods: Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide.
Results: The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01).
Conclusions: Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.