Impact of Haemophilus influenzae Type b Polysaccharide-Tetanus Protein Conjugate Vaccine on Responses to Concurrently Administered Diphtheria-Tetanus-Pertussis Vaccine
- John D. Clemens, MD;
- Catterine Ferreccio, MD, MPH;
- Myron M. Levine, MD, DTMH;
- Isidoro Horwitz, MD;
- Malla R. Rao, M Eng;
- Kathryn M. Edwards, MD;
- Bernard Fritzell, MD
- From the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore (Drs Clemens, Ferreccio, and Levine, and Mr Rao); Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md (Dr Clemens and Mr Rao); Ministry of Health, Republic of Chile (Dr Ferreccio); Department of Pediatrics, Roberto del Rio Hospital, Santiago (Dr Horwitz); Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn (Dr Edwards); and Pasteur Mérieux Sérums et Vaccins, Marcy l'Etoile, France (Dr Fritzell).
Abstract
Objective. —To assess whether serum antibody responses to diphtheriatetanus-pertussis (DTP) vaccine were affected by coadministration of Haemophilus influenzae type b capsular polyribosylribitol phosphate polysaccharide-tetanus protein (PRP-T) conjugate vaccine when given to patients at 2, 4, and 6 months of age.
Design. —Randomized, double-blind clinical trial.
Setting. —Urban Santiago, Chile.
Patients. —Healthy infants assembled from health centers. Two hundred seventy-eight (74%) of 375 eligible infants participated; 222, who complied with the complete protocol, constituted the primary group under analysis.
Interventions. —One of three vaccine regimens was given to study participants at 2,4, and 6 months of age, either DTP mixed in the same syringe as PRP-T (group 1); DTP and PRP-T given at separate injection sites (group 2); or DTP without PRP-T (group 3).
Primary Outcome Measures. —Titers of serum antidiphtheria toxoid, antitetanus toxoid, and pertussis agglutinin antibodies were measured in blood samples taken from patients 2 months after each dose.
Results. —Serum antidiphtheria toxoid and antitetanus toxoid responses showed no important depressions in the patients receiving PRP-T. In contrast, geometric mean titers (GMTs) of pertussis agglutinins, expressed as reciprocal serum dilutions, after both the second and third doses (GMT2, GMT3) were lowest in group 1 (GMT2 = 89; GMT3 = 1230), intermediate in group 2 (GMT2 = 123; GMT3 = 1995), and highest in group 3 (GMT2 = 210; GMT3=3090; P<.05 for trend group 1<group 2<group 3 after each dose). Antipertussis toxin and antipertussis filamentous hemagglutinin antibody titers also were depressed in patients who received PRP-T. Follow-up of a subset at 18 months revealed an expected decline of pertussis agglutinin titers to near baseline levels in each group.
Conclusions. —Concurrent administration of PRP-T vaccine with DTP vaccine, either in the same syringe or at different sites, interfered with antipertussis responses to a primary series of immunizations. Although the clinical significance of this antagonism is uncertain, these data underscore the caution required in decisions to add new vaccines to existing immunization regimens.
(JAMA. 1992;267:673-678)
Footnotes
-
Reprint requests to Division of Epidemiology, Biostatistics, and Prevention Research, National Institute of Child Health and Human Development, Executive Plaza North-640, Bethesda, MD 20892 (Dr Clemens).
