XB, JAW, DT, AB and NG performed the study

XB, JAW, DT, AB and NG performed the study. vaccination. 4CMenB coverage was defined as the percentage of strains with positive killing (hSBA titres ?4 after immunisation and negative baseline hSBA titres ?2). Coverage of 4CMenB was 40.0% (95% confidence interval [CI]: 24.9C56.7) and 87.5% (95%CI: 73.2C95.8) at one month post-primary and booster vaccination, respectively, regardless of immunisation schedule. Using a more conservative threshold (post-immunisation hSBA titres ?8; baseline ?2), at one month post-booster dose, strain coverages were 80% (3?+?1) and 70% (2?+?1). We used a linear regression model to assess correlation between post-immunisation hSBA data for each strain in the two groups; Pearsons correlation coefficients were 0.93 and 0.99 at one month post-primary and booster vaccination. Overall, there is no evidence for a difference in strain coverage when 4CMenB is administered according to a 3?+?1 or 2 2?+?1 infant vaccination schedule. adhesin Rabbit Polyclonal to CLIC6 A and Neisserial heparin-binding antigen) and the outer membrane vesicles of the New Zealand outbreak strain (NZ 98/254). The vaccine has already been shown to be immunogenic and well tolerated in all age groups,6 including infants, children and adolescents.7,8 Currently, 4CMenB is approved for use in infants in 39 countries including European countries, Canada, Australia, Chile, Uruguay, Argentina and Brazil9 as a 3?+?1 schedule, with primary doses administered in the first six months of life, and a booster dose at 12C23?months of age. In the United Kingdom (UK), 4CMenB was introduced in the national immunisation schedule in 2015 as a 2?+?1-dose series administered at 2, 4 and 12?months of age, which was considered cost-effective based on modelling data.10 A vaccine effectiveness of 82.9% was estimated against all serogroup B disease and 94.2% against vaccine-preventable group B strains, as measured during the first 10?months of the national immunisation programme, i.e. following the two-dose primary series.11 A previous clinical GSK2578215A study comparing the administration of 4CMenB according to a 3?+?1 schedule (at 2.5, 3.5, 5, 11?months of age) with a reduced 2?+?1 (at 3.5, 5, 11?months of age) schedule in infants showed that the vaccine was safe and immunogenic.7 The immune response was evaluated by serum bactericidal antibody with human complement (hSBA) of individual sera against four indicator serogroup B strains; the bactericidal response GSK2578215A induced by sera deriving from both immunisation schedules was comparable.7 The ability of 4CMenB to cover genetically diverse strains is predicted by the Meningococcal Antigen Typing System (MATS) assay, an enzyme-linked immunosorbent assay GSK2578215A (ELISA) which measures the level of expression and the sequence diversity of each of the 4CMenB antigens in a given strain.12 Strains are predicted to be killed in the hSBA when their MATS relative potency (the ELISA reactivity GSK2578215A compared to that of a reference serogroup B strain) is higher than the positive bactericidal threshold, specific for each antigen. This correlation has been defined by testing the killing ability of antibodies in infant sera derived from a 3?+?1 immunisation schedule on a panel of 57 genetically diverse strains.12 Due to the large number of circulating serogroup B strains, the MATS assay has been applied to strains isolated from a specific region or country to assess the potential breadth of coverage conferred by 4CMenB, and to anticipate the impact of vaccination on the local IMD burden. The estimated strain coverage was between 66% and 91%, depending on the epidemiology of serogroup B IMD in each country.13 However, prediction based on MATS can underestimate the strain coverage afforded by 4CMenB, because the method is based on single antigens and does not account for synergistic effects of antibodies directed against different antigens, nor for the contribution of antibodies against minor outer membrane antigens to complement-mediated bacterial killing. This has been clearly demonstrated by analysing a panel of 40 serogroup B strains representative of 535 strains isolated in England and Wales in 2007C2008, tested using the hSBA assay on pooled sera of infants (following a 3?+?1 vaccination series) and adolescents which showed higher strain coverage compared to MATS.14 This study compares the bactericidal activity of sera from a clinical trial carried out in infants receiving 4CMenB according to either the 3?+?1 or 2 2?+?1 vaccination schedule,7 to assess whether differences in the number of doses and the immunisation regimen would lead to differences in strain coverage. For this purpose, the panel of 40 previously characterised UK serogroup B strains was tested using the hSBA. A summary contextualizing the results, the potential clinical research relevance and the impact of our study is.