Immunogenicity of a Fourth Dose of Haemophilus influenzae Type b (Hib) Conjugate Vaccine and Antibody Persistence in Young Children from the United Kingdom Who Were Primed with Acellular or Whole-Cell Pertussis Component-Containing Hib Combinations in Infancy

Abstract

In response to the rising incidence of Haemophilus influenzae type b (Hib) disease in the United Kingdom, a national campaign to give a booster dose of single-antigen Hib conjugate vaccine to children aged 6 months to 4 years was undertaken in 2003. Children (n ‫؍‬ 386) eligible for Hib vaccine in the campaign were recruited. Hib antibody concentrations were measured before boost and at 1 month, 6 months, 1 year, and 2 years after boost and were analyzed according to children's ages at booster dose and whether a Hib combination vaccine containing acellular pertussis (aP) or whole-cell pertussis (wP) components was given in infancy. The geometric mean antibody concentrations (GMCs) before the booster declined as the time since primary immunization increased (P < 0.001), and GMCs were threefold higher in recipients of wP-Hib than aP-Hib combination vaccines (P < 0.001). GMCs 1 month after the booster increased with age (P < 0.001) as follows: 6 to 11 months; 30 g/ml (95% confidence interval [CI], 22 to 40); 12 to 17 months, 68 g/ml (95% CI, 38 to 124); and 2 to 4 years, 182 g/ml (151 to 220), with no difference according to the type of priming vaccine received. Antibody levels declined after the booster, but 2 years later, GMCs were more than 1.0 g/ml for all age groups. By extrapolating data for the decline in antibody levels, we found the GMCs 4 years after boosting were predicted to be 0.6, 1.4, and 2.6 g/ml for those boosted at 6 to 11 months, 12 to 17 months, and 2 to 4 years, respectively, with levels of at least 0.15 g/ml in about 90% of individuals. A booster dose of Hib vaccine given after the first year of life should provide long-lasting protection.

Kinetics of Antibody Persistence following Administration of a Combination Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine in Healthy Infants in the United Kingdom Primed with a Monovalent Meningococcal Serogroup C Vaccine

“…This relatively poor antibody persistence was surprising, although to date, the kinetics of antibody persistence of meningococcal antibodies have not been studied. The proportions of subjects maintaining protective levels of antibodies after the administration of other conjugate vaccines such as Hib are more satisfactory following boosting, as demonstrated in this study and elsewhere (17,18). As the rate of antibody decay is similar for both PRP IgG (Ϫ1.00) and meningococcal serogroup C IgG (Ϫ0.95) following boosting, the actual magnitude of the booster response appears to determine persistence; the PRP IgG GMCs were substantially higher than the serogroup C IgG GMCs 1 month following boosting.…”

“…Comparison of the antibody kinetics with boosting (the present study) and without boosting (17) in the second year of life showed similar decay patterns (changes in the log SBA titer per log 10 unit of time, Ϫ1.60 and Ϫ1.55, respectively) (Fig. 1).…”

“…Previously unpublished antibody persistence data for children given three primary doses of an MCC vaccine (either NeisVac-C, Meningitec, or Menjugate) at 2, 3, and 4 months of age but who were not given a booster were available from an earlier study (17) and were compared with the MCC persistence data obtained after the Menitorix boosting in the current study. In the earlier study, infants received three doses of a Hib-containing vaccine in infancy, and some of those infants were boosted with a single-antigen Hib-TT vaccine (Hiberix; GSK) in the second year of life.…”

Naturally Acquired and Conjugate Vaccine-Induced Antibody to Haemophilus influenzae Type b (Hib) Polysaccharide in Malian Children: Serological Assessment of the Hib Immunization Program in Mali

“…Consequently, infants immunized with wP/PRP-T compared with aP/PRP-T have stronger responses, better persistence of anti-PRP antibodies, and less risk of vaccine failure. 51 These boosting factors may decrease in the future as widespread Hib vaccination and improved socioeconomic conditions (decreased crowding) progressively diminish upper respiratory carriage of Hib. 11,52 They would also be lower if in the future acellular pertussis vaccine came to replace whole cell pertussis in the infant combination vaccine.…”

Updated Postlicensure Surveillance of the Meningococcal C Conjugate Vaccine in England and Wales: Effectiveness, Validation of Serological Correlates of Protection, and Modeling Predictions of the Duration of Herd Immunity

“…Predicted vaccine effectiveness was calculated using rSBA persistence data from a clinical trial in children who received the MCC vaccine in infancy at 2, 3, and 4 months of age (from 2000 to 2003) and from whom blood samples were taken before and 4 weeks after a Hib booster dose given between 6 months and 4 years of age (30). rSBA titers were measured for these samples as previously described (6,8).…”