Dm. Granoff et al., EFFECT OF CARRIER PROTEIN PRIMING ON ANTIBODY-RESPONSES TO HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN INFANTS, JAMA, the journal of the American Medical Association, 272(14), 1994, pp. 1116-1121
Objective.-To assess the effect of priming with diphtheria and tetanus
toroid vaccine (DT) at 1 month of age on the anticapsular polyribosyl
ribitol phosphate (PRP) antibody responses of infants vaccinated with
Haemophilus influenzae type b polysaccharide-tetanus toroid conjugate
(PRP-T) or PRP oligosaccharide-cross-reactive mutant diphtheria toxin
conjugate (HbOC). Design.-Randomized controlled trial with serum sampl
es assayed blindly. Participants and Setting.-Healthy infants enrolled
in private pediatric practices; 94 (91%) of 103 infants had prevaccin
ation and postvaccination serum samples available for analysis. Interv
entions.-Two groups received DT vaccination at 1 month of age and subs
equent injections of PRP-T or HbOC conjugate vaccines at 2, 4, and 6 m
onths of age. The control groups were not vaccinated with DT but recei
ved PRP-T or HbOC at the same ages as the carrier-primed groups. Infan
ts in all groups were given a booster injection of unconjugated PRP at
12 months of age to assess induction of immunologic memory. Main Outc
ome Measure.-Concentrations of serum antibody to PRP. Main Results.-Th
e DT-primed infants given PRP-T had twofold to threefold higher geomet
ric mean anti-PRP antibody responses after one (P less than or equal t
o.01), two (P less than or equal to.01), or three (P=.06) doses of con
jugate vaccine than the infants of the unprimed group. The primed infa
nts also had threefold higher memory antibody responses to the booster
PRP injection given at 12 months of age (concentration of 24.4 vs 8.4
mu g/mL in infants not primed with DT; P<.01). The DT-primed infants
given HbOC had twofold to threefold higher antibody responses after on
e (P=.07) or two (P<.01) doses of conjugate vaccine than the unprimed
HbOC group, but there were no significant differences after the third
dose of conjugate vaccine or after the PRP booster injection. Conclusi
ons.-Vaccination with DT at 1 month of age increases the magnitude of
the anti-PRP antibody responses to conjugate vaccination. With HbOC, t
he effect of carrier priming was present for up to 6 months of age, wh
ereas in infants vaccinated with PRP-T, enhanced immunity was present
for at least 12 months.