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Effect of Carrier Protein Priming on Antibody Responses to Haemophilus influenzae Type b Conjugate Vaccines in Infants
Dan M. Granoff, MD;
Sandra J. Holmes, PhD, MHA;
Robert B. Belshe, MD;
Michael T. Osterholm, PhD, MPH;
Joseph E. McHugh, MD;
Edwin L. Anderson, MD
JAMA. 1994;272(14):1116-1121.
Abstract
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Objective.
—To assess the effect of priming with diphtheria and tetanus toxoid vaccine (DT) at 1 month of age on the anticapsular polyribosylribitol phosphate (PRP) antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide—tetanus toxoid conjugate (PRP-T) or PRP oligosaccharide— cross-reactive mutant diphtheria toxin conjugate (HbOC).
Design.
—Randomized controlled trial with serum samples assayed blindly.
Participants and Setting.
—Healthy infants enrolled in private pediatric practices; 94 (91%) of 103 infants had prevaccination and postvaccination serum samples available for analysis.
Interventions.
—Two groups received DT vaccination at 1 month of age and subsequent injections of PRP-T or HbOC conjugate vaccines at 2,4, and 6 months of age. The control groups were not vaccinated with DT but received PRP-T or HbOC at the same ages as the carrier-primed groups. Infants in all groups were given a booster injection of unconjugated PRP at 12 months of age to assess induction of immunologic memory.
Main Outcome Measure.
—Concentrations of serum antibody to PRP.
Main Results.
—The DT-primed infants given PRP-T had twofold to threefold higher geometric mean anti-PRP antibody responses after one (P .01), two (P.01), or three (P=.06) doses of conjugate vaccine than the infants of the unprimed group. The primed infants 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 µg/mL in infants not primed with DT; P<.01). The DT-primed infants given HbOC had twofold to threefold higher antibody responses after one (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.
Conclusions.
—Vaccination with DT at 1 month of age increases the magnitude of the anti-PRP antibody responses to conjugate vaccination. With HbOC, the effect of carrier priming was present for up to 6 months of age, whereas in infants vaccinated with PRP-T, enhanced immunity was present for at least 12 months.
(JAMA. 1994;272:1116-1121)
Author Affiliations
From the Division of Infectious Diseases, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, Mo (Dr Granoff); the National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Holmes); the National Institute of Allergy and Infectious Diseases Vaccine Evaluation Unit, Departments of Pediatrics and Medicine, St Louis (Mo) University School of Medicine (Drs Belshe and Anderson); the Acute Disease Epidemiology Section, Minnesota Department of Health, Minneapolis (Dr Osterholm); and the Wayzata (Minn) Children's Clinic (Dr McHugh). Dr Granoff is executive director of Biocene Clinical Research, Chiron Corporation, Emeryville, Calif, and research scientist at Children's Hospital Oakland (Calif) Research Institute.
Footnotes
This work was presented, in part, at the annual meeting of the Society for Pediatric Research, Washington, DC, May 5, 1993.
Reprint requests to Children's Hospital Oakland Research Institute, 747 52nd St, Oakland, CA 94609 (Dr Granoff).
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