Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom

JAMA. 2000 Nov 8;284(18):2334-40. doi: 10.1001/jama.284.18.2334.


Context: The schedule for Haemophilus influenzae type b (Hib) vaccination of infants in the United Kingdom consists of 3 doses given at 2, 3, and 4 months of age. Many countries include a fourth dose (booster) of Hib vaccine in the second year of life on the basis of declining Hib antibody concentrations after the primary series. Few data are available to show that this fourth dose is actually necessary.

Objective: To evaluate long-term clinical protection against Hib disease and Hib antibody concentrations following primary Hib vaccination without a booster dose.

Design, setting, and subjects: Clinical protection study conducted between October 1992 and March 1999 in the United Kingdom, in which children developing invasive Hib disease despite vaccination in infancy with 3 doses of Hib conjugate vaccine were reported by pediatricians through an active, prospective, national survey. Separate antibody studies were conducted among 2 cohorts of children (n = 153 and n = 107) vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccine and followed up to 43 and 72 months of age.

Main outcome measures: Age-specific vaccine effectiveness, derived from the observed number of true vaccine failures after 3 Hib vaccine doses compared with the number of cases expected based on the age-specific rates of invasive Hib disease obtained prior to the introduction of Hib vaccines; and proportion of children in the 2 cohorts with Hib antibody concentrations of less than 0.15 and less than 1.0 microg/mL.

Results: Ninety-six true vaccine failures occurring after 3 vaccine doses were detected. During the study period, an estimated 4,368,200 infants in the United Kingdom received 3 doses of vaccine; therefore, the vaccine failure rate was 2.2 per 100,000 vaccinees (95% confidence interval, 1.8-2.7 per 100,000). Although vaccine effectiveness declined significantly after the first year of life (P<.001), it remained high until the sixth year of life (99.4% in children aged 5-11 months vs 97.3% in those aged 12-71 months). The proportion of cohorts 1 and 2 with anti-PRP antibody levels of less than 0.15 microg/mL increased between 12 and 72 months of age (6% at 12 months, 8% at 43 months, and 32% at 72 months; chi(2)(1) = 18.25; P<.001 for trend).

Conclusions: Our results suggest that anti-PRP antibody levels and clinical protection against Hib disease wane over time after Hib vaccination at 2, 3, and 4 months of age without a booster dose at 2 years of age. The decline in clinical protection is minimal, however, suggesting that a booster dose of Hib vaccine following infant vaccination is not essential. JAMA. 2000;284:2334-2340.

MeSH terms

  • Antibodies, Bacterial / biosynthesis*
  • Child
  • Child, Preschool
  • Haemophilus Infections / epidemiology
  • Haemophilus Infections / prevention & control*
  • Haemophilus Vaccines / administration & dosage
  • Haemophilus Vaccines / immunology*
  • Haemophilus influenzae type b / immunology*
  • Humans
  • Immunization Schedule
  • Immunization, Secondary
  • Infant
  • Polysaccharides / immunology
  • Polysaccharides, Bacterial / immunology
  • Treatment Failure
  • United Kingdom / epidemiology
  • Vaccination
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology


  • Antibodies, Bacterial
  • Haemophilus Vaccines
  • Polysaccharides
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate
  • polyribitol phosphate