Haemophilus influenzae Type b Reemergence after Combination Immunization

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.

Section: Discussionsupporting

confidence: 79%

“…Johnson et al measured antibody concentrations in 2 to 4 year olds prior to their receiving a booster in the 2003 campaign; the GMC in DTwP/Hib recipients was 0.61 g/ml (95% CI, 0.41 to 0.92), compared with 0.30 g/ml (95% CI, 0.19 to 0.49) in DTaP/Hib recipients (11). These levels are remarkably close to those reported here.…”

Section: Discussionsupporting

confidence: 62%

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

Southern¹,

McVernon

Gelb

et al. 2007

“…It was also observed, in the Myanmar study, that anti-PRP antibody GMCs were considerably higher following DTPw-based Hib vaccinations, which we may attribute to the use of whole-cell pertussis, which was already known to elicit higher antibody titers than acellular pertussis (11). However, after the booster dose, these differences between vaccines were no longer present, in line with a recent study in which there was no association between postbooster anti-PRP antibody concentrations and the vaccine (DTPw/Hib and/or DTPa/Hib) used for primary vaccination (15). On the other hand, the DTPa/Hib Germany A and B studies demonstrated lower postbooster antibody levels for the DTPa/Hib combination than with separate administration (Table 2).…”

Section: Discussionsupporting

confidence: 66%

Quality of theHaemophilus influenzaeType b (Hib) Antibody Response Induced by Diphtheria-Tetanus-Acellular Pertussis/Hib Combination Vaccines

Denoël

Green

Vleeschauwer

et al. 2007

“…The United Kingdom's experience with Hib vaccine established the importance of a reduction in carriage (3,16,20) and induction of herd immunity in the long-term control of disease. MCC immunization has been shown to significantly reduce nasopharyngeal carriage of serogroup C meningococci (18) for at least 2 years with no evidence of serogroup replacement (19).…”

Section: Discussionmentioning

confidence: 99%

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

Campbell

Andrews

Borrow

et al. 2010

196

133

Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, ؊63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016.