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

• Published in: Clinical infectious diseases Vol. 46; no. 2; pp. 186 - 192
• Main Authors: Lee, Yeh Chen, Kelly, Dominic F., Yu, Ly-Mee, Slack, Mary P. E., Booy, Robert, Heath, Paul T., Siegrist, Claire-Anne, Moxon, Richard E., Pollard, Andrew J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.01.2008; University of Chicago Press; Oxford University Press
• Subjects: Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antibody affinity; Antibody Affinity - immunology; Articles and Commentaries; Bacterial Capsules; Biological and medical sciences; Child, Preschool; Children; Children & youth; Cohort Studies; Comparative analysis; Conjugate vaccines; Disease Susceptibility; Female; General aspects; Haemophilus Infections - blood; Haemophilus Infections - immunology; Haemophilus Infections - microbiology; Haemophilus Infections - prevention & control; Haemophilus influenzae; Haemophilus influenzae type b; Haemophilus influenzae type b - immunology; Haemophilus Vaccines - immunology; Haemophilus Vaccines - therapeutic use; Human infectious diseases. Experimental studies and models; Humans; Immune response; Infant; Infections; Infectious diseases; Influenza; Male; Medical sciences; Pediatrics; Polysaccharides; Polysaccharides, Bacterial - immunology; Polysaccharides, Bacterial - therapeutic use; Retrospective Studies; Studies; Treatment Failure; Vaccination; Vaccines; Vaccines, Conjugate - immunology; Vaccines, Conjugate - therapeutic use; United Kingdom > UK; Human; Pasteurellaceae; Prevention; Immunoprophylaxis; Antibody; Pathogenesis; Quality; Bacteria; Vaccine; Child; Failure; Haemophilus influenzae
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/524668

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.