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

Journal article

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.

Authors: Lee, Y; Kelly, D; Yu, L; Slack, M; Booy, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: University of Chicago Press
• Journal: Clinical Infectious Diseases
• Volume: 46
• Issue: 2
• Pages: 186-192
• Publication date: 2008-01-01
• Edition: Publisher's version
• DOI: 10.1086/524668
• ISSN: 1058-4838
• Language: English
• Keywords: Haemophilus influenzae type b (Hib); vaccine
• Subjects: Vaccinology; Infectious diseases; Paediatrics; Statistics (see also social sciences)