Impact of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanus-pertussis vaccine.
OBJECTIVE
To assess whether serum antibody responses to diphtheria-tetanus-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.


METHODS
Randomized, double-blind clinical trial.


METHODS
Urban Santiago, Chile.


METHODS
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.


METHODS
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).


METHODS
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 less than .05 for trend group 1 less than group 2 less than 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.
Clemens
J D
JD
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.
Ferreccio
C
C
Levine
M M
MM
Horwitz
I
I
Rao
M R
MR
Edwards
K M
KM
Fritzell
B
B
D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001428:Bacterial Vaccines / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology; D003017:Clostridium tetani / Q000276:immunology; D003353:Corynebacterium diphtheriae / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D013745:Tetanus Toxoid / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D013745:Tetanus Toxoid