Lagging Immune Response to Haemophilus influenzae Serotype b (Hib) Conjugate Vaccine after the Primary Vaccination with Hib of Infants in The Netherlands.

In 1993, a Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in the Dutch national immunization program, resulting in a sharp decrease in invasive Hib disease. We used a population-based set of serum samples collected in the Netherlands in 2006-2007 (Pienter-II, 5696 sera) to assess the concentration of antibodies to the capsular polysaccharide of Hib, and compared the results with those obtained from a similar set collected in 1995-1996 (Pienter-I, 7837 sera). Post-primary vaccination serum samples from children aged 6-11 months from the Pienter-II study contained approximately 4-fold lower anti-Hib antibody concentrations than samples from children from the Pienter-I study. No such difference was found in post-booster samples from children older than 11 months of age. In Pienter-II, the proportion of children aged 6-11 months with anti-Hib antibody concentrations below the putative protective concentration of 0.15 µg/mL was 30%, which is significantly higher than in the Pienter-I study (12%). Fewer children in the Pienter-II group developed antibodies able to kill Hib in a serum bactericidal assay compared to the Pienter-I children. The cause of the lagged response in Pienter-II children remain uncertain, but lack of natural boosting, interference by the acellular pertussis vaccine, combining vaccines and acceleration of the schedule may have contributed.