Scientific article
English

Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody

Published inClinical infectious diseases, vol. 46, no. 2, p. 186-192
Publication date2008
Abstract

BACKGROUND: Despite the excellent immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines, breakthrough cases of Hib disease still affect a small proportion of vaccinated children in the United Kingdom. We performed a retrospective study to compare the avidity of antibody directed against the Hib polysaccharide capsule (PRP) in children who experienced Hib vaccine failure in the United Kingdom among 3 historical cohorts and with age-matched healthy control subjects. METHODS: Serum samples from vaccinated children with invasive Hib disease were collected beginning in 1992 as part of enhanced surveillance for Hib disease following vaccine introduction. A total of 251 children who experienced Hib vaccine failure were identified from 3 historical cohorts (1992-1995, 1996-1999, and 2000-2003). The anti-PRP antibody concentration and avidity from healthy age-matched control subjects was obtained for the 3 contemporary time points (1995, 1999, and 2002). Serum anti-PRP antibody concentration was measured in each of the samples using a standard Hib ELISA, and antibody avidity was determined using thiocyanate elution. RESULTS: Within the first 60 days after disease onset, there was no change in the anti-PRP antibody avidity, and there was no statistically significant difference in the geometric mean Hib antibody avidity over the 3 study periods. However, the children who experienced Hib vaccine failure had significantly lower Hib antibody avidity than did healthy control subjects, despite a marked antibody response following infection. CONCLUSIONS: Children who experience Hib disease despite vaccination appear to have a defect in immunological priming, leading to a qualitative difference in Hib-specific memory B cells. Low anti-PRP antibody avidity decreases the functional activity of anti-PRP antibody in the sera of these children experiencing vaccine failure, leading to disease susceptibility.

Keywords
  • Antibodies, Bacterial/blood/immunology
  • Antibody Affinity/immunology
  • Bacterial Capsules
  • Child, Preschool
  • Cohort Studies
  • Disease Susceptibility
  • Female
  • Haemophilus Infections/blood/immunology/microbiology/prevention & control
  • Haemophilus Vaccines/immunology/therapeutic use
  • Haemophilus influenzae type b/immunology
  • Humans
  • Infant
  • Male
  • Polysaccharides, Bacterial/immunology/therapeutic use
  • Retrospective Studies
  • Treatment Failure
  • Vaccines, Conjugate/immunology/therapeutic use
Citation (ISO format)
LEE, Yeh Chen et al. Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. In: Clinical infectious diseases, 2008, vol. 46, n° 2, p. 186–192. doi: 10.1086/524668
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
Journal ISSN1058-4838
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