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

Lee, Yeh Chen
Kelly, Dominic F.
Yu, Ly-Mee
Slack, Mary P E.
Booy, Robert
Heath, Paul T.
Moxon, Richard E.
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Published in Clinical Infectious Diseases. 2008, vol. 46, no. 2, p. 186-92
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/immunologyAntibody Affinity/immunologyBacterial CapsulesChild, PreschoolCohort StudiesDisease SusceptibilityFemaleHaemophilus Infections/blood/immunology/microbiology/prevention & controlHaemophilus Vaccines/immunology/therapeutic useHaemophilus influenzae type b/immunologyHumansInfantMalePolysaccharides, Bacterial/immunology/therapeutic useRetrospective StudiesTreatment FailureVaccines, Conjugate/immunology/therapeutic use
PMID: 18171249
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Research group Centre de Vaccinologie et d'Immunologie néonatale (177)
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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. 186-92. https://archive-ouverte.unige.ch/unige:2512

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Deposited on : 2009-08-27

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