Journal Article

<i>Haemophilus influenzae</i> Type b Vaccine Failure in Children Is Associated with Inadequate Production of High-Quality Antibody

Yeh Chen Lee, Dominic F. Kelly, Ly-Mee Yu, Mary P. E. Slack, Robert Booy, Paul T. Heath, Claire-Anne Siegrist, Richard E. Moxon and Andrew J. Pollard

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 46, issue 2, pages 186-192
Published in print January 2008 | ISSN: 1058-4838
Published online January 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/524668
Haemophilus influenzae Type b Vaccine Failure in Children Is Associated with Inadequate Production of High-Quality Antibody

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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.

Journal Article.  3380 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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