Research in context
Evidence before this study
We searched PubMed with the terms “4CMenB”, “Bexsero”, “meningococcal serogroup B vaccine”, and any combination of “vaccine effectiveness” or “impact”. Publication dates and languages were not limited. Our search results identified no data for the vaccine effectiveness or impact of 4CMenB against invasive meningococcal group B (MenB) disease.
In January, 2013, 4CMenB was licensed in Europe on immunogenicity and safety studies only. The vaccine induces bactericidal antibodies that target the respective antigens, which could be absent or variably expressed on the surface of different meningococci. Because 4CMenB contains multiple recombinant proteins in addition to the outer membrane vesicle, antibody concentrations or bactericidal activity against individual vaccine antigens do not reliably predict in-vitro killing of meningococci. For this reason, the Meningococcal Antigen Typing System (MATS) was developed to screen large numbers of meningococcal strains and predict whether they would be killed by 4CMenB-induced antibodies. MATS is a qualitative and quantitative ELISA that quantifies expression of the vaccine-associated antigens (fHbp, NHBA, and NadA) in combination with the ability of 4CMenB-induced antibodies to recognise these proteins on the surface of individual meningococcal isolates. For an isolate to be MATS positive, antibodies against at least one vaccine antigen must exceed the positive bactericidal threshold, which is assigned on the basis of killing using postvaccination sera from infants after their 12-month booster, or the isolate must possess homologous PorA (P1.4). In England and Wales, MATS predicted that 73% (95% CI 57–87%) of invasive MenB disease isolates in 2007–08 would be killed by vaccine-induced antibodies in infants. In a serum bactericidal antibody assay with human complement (hSBA), however, pooled sera from infants and adolescents immunised with 4CMenB killed 88% of a representative sample of MenB disease isolates from England and Wales during 2007–08. In the cost-effectiveness analysis, therefore, 4CMenB was predicted to protect against 73–88% of circulating MenB strains in the UK.
Compared with adolescents and adults, infants have lower cross-protection against MenB strains that are predicted by MATS to be non-vaccine preventable. Data from a recent university-associated MenB outbreak in the USA showed that sera from a third of 499 adolescents who received two doses of 4CMenB 10 weeks apart were unable to kill the outbreak strain using the hSBA assay, even though the outbreak strain was predicted by MATS to express two vaccine antigens.
Added value of this study
The UK is the first country to introduce 4CMenB into a publicly funded, national immunisation programme. In England, vaccine coverage was high in all eligible cohorts, reaching 95·5% for one dose and 88·6%% for two doses. During the first 10 months of the programme, two-dose vaccine effectiveness of 82·9% against all MenB disease was equivalent to a vaccine effectiveness of 94·2% against vaccine-preventable MenB strains. By the end of June, 2016, MenB cases in vaccine-eligible infants had halved, irrespective of the infants’ vaccination status or expected vaccine strain coverage.
Implication of all the available evidence
We have provided the first evidence of protection against group B meningococcal disease conferred by the novel, multicomponent 4CMenB vaccine in infants. While ongoing national surveillance will continue to monitor the longer-term impact of the programme, these findings represent a step forward in the battle against meningococcal disease and will help reassure that the vaccine protects against this deadly infection.