Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom

Context The schedule for Haemophilus influenzae type b (Hib) vaccination of infants in the United Kingdom consists of 3 doses given at 2, 3, and 4 mon ths of age. Many countries include a fourth dose (booster) of Hib vaccine i n the second year of life on the basis of declining Hib antibody concentrat ions after the primary series. Few data are available to show that this fou rth dose is actually necessary. Objective To evaluate long-term clinical protection against Hib disease and Hib antibody concentrations following primary Hib vaccination without a bo oster dose. Design, Setting, and Subjects Clinical protection study conducted between O ctober 1992 and March 1999 in the United Kingdom, in which children develop ing invasive Hib disease despite vaccination in infancy with 3 doses of Hib conjugate vaccine were reported by pediatricians through an active, prospe ctive, national survey. Separate antibody studies were conducted among 2 co horts of children (n=153 and n=107) vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccine and followed up to 43 and 72 months of age. Main Outcome Measures Age-specific vaccine effectiveness, derived from the observed number of true vaccine failures after 3 Hib vaccine doses compared with the number of cases expected based on the age-specific rates of invas ive Hib disease obtained prior to the introduction of Hib vaccines; and pro portion of children in the 2 cohorts with Hib antibody concentrations of le ss than 0.15 and less than 1.0 mug/mL. Results Ninety-six true vaccine failures occurring after 3 vaccine doses we re detected. During the study period, an estimated 4368200 infants in the U nited Kingdom received 3 doses of vaccine; therefore, the vaccine failure r ate was 2.2 per 100000 vaccinees (95% confidence interval, 1.8-2.7 per 1000 00). Although vaccine effectiveness declined significantly after the first year of life (P<.001), it remained high until the sixth year of life (99.4% in children aged 5-11 months vs 97.3% in those aged 12-71 months). The pro portion of cohorts 1 and 2 with anti-PRP antibody levels of less than 0.15 <mu>g/mL increased between 12 and 72 months of age (6% at 12 months, 8% at 43 months, and 32% at 72 months; chi (2)(1)=18.25; P<.001 for trend). Conclusions Our results suggest that anti-PRP antibody levels and clinical protection against Hib disease wane over time after Hib vaccination at 2, 3 , and 4 months of age without a booster dose at 2 years of age. The decline in clinical protection is minimal, however, suggesting that a booster dose of Hib vaccine following infant vaccination is not essential.