First Real-world Evidence of Meningococcal Group B Vaccine, 4CMenB, Protection Against Meningococcal Group W Disease: Prospective Enhanced National Surveillance, England

Abstract

BACKGROUND 4CMenB is a protein-based meningococcal group B vaccine but the vaccine antigens may also be present on non-group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunisation programme, alongside an emergency adolescent meningococcal ACWY (MenACWY) programme to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST11 clonal complex. The adolescent programme aimed to provide direct protection for adolescents and, over time, indirect (herd) protection across the population. METHODS Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during four years before and four years after implementation of both vaccines were analysed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB programme on top of the indirect impact of the adolescent MenACWY programme in children eligible for 4CMenB but not MenACWY. RESULTS Model estimates showed 69% (adjusted incidence rate ratio (IRR) 0.31, 95%CI, 0.20-0.67) and 52% (aIRR 0.48, 95%CI 0.28-0.81) fewer MenW cases than predicted among age-cohorts that were fully-eligible and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in &5 year-olds. 4CMenB directly prevented 98 (95%CI, 34-201) cases, while the MenACWY programme indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over four years. Disease severity was similar in 4CMenB-immunised and unimmunised children. CONCLUSIONS Our results provide the first real-world evidence of the direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups.

Recent advances in meningococcal B disease prevention: real-world evidence from 4CMenB vaccination

“…The 4CMenB program prevented 98 cases of MenW IMD in infants and young children over the first 4 years. 54 These observations are supported by 2 in vitro studies; high levels of bactericidal activity against 6 clinical MenW isolates from England and Wales in sera from 4CMenB-vaccinated individuals, suggesting cross-reactivity due to surface proteins common to both serogroups. 52 A study with sera from 4CMenB-vaccinated infants demonstrated bactericidal killing of 74% of a panel of MenC, MenW and MenY clinical isolates representing a range of clonal complexes.…”

“…77 4CMenB also demonstrates a statistically significant impact in preventing MenW IMD. 54 The potentially wider impacts of 4CMenB on non-MenB/non-MenW disease have yet to be quantified. Of particular interest is whether 4CMenB can also prevent infections due to N. gonorrhoeae which shares 80-90% genetic homology with MenB.…”

Lessons for and from the COVID-19 pandemic response — An appraisal of guidance for the public health management of Invasive Meningococcal Disease

“…Guideline development and revision should also be considered frequently within a global context, ideally with the introduction of new vaccines or vaccination programs, as it becomes increasingly evident that inconsistent management of an infectious disease, either within or between country jurisdictions, can hinder effective disease management. Although conjugate meningococcal vaccines show evidence of reduction in transmission [ 13 ], they do not affect overall carriage rates [ 40 ]. As new vaccines are developed and implemented in population-wide programs, guidelines for management of contacts need to be reviewed to ensure they remain contemporaneous.…”

“…IMD is a severe disease caused by Neisseria meningitidis ( N. meningitidis ), a bacteria found in the human nasopharyngeal mucosa, the cells lining the back of the nose and throat [ 5 ]. The disease has a rapid onset and cases require prompt antibiotic treatment to prevent mortality [ 12 , 13 ]. Survivors of IMD often suffer from serious long-term sequalae, including - but not limited to - loss of limbs, neurological damage, hearing loss and physical or psychological scarring [ 6 ].…”

“…IMD is preventable through vaccination, with vaccines available to cover five of the six most common disease-causing strains (A, B, C, X, Y, and W) [ 4 , [10] , [11] , [12] , [13] ]. Carriage of N. meningitidis can be prevented through the use of clearance antibiotics (chemoprophylaxis), for contacts of cases – that is, those people who have had close and sustained interactions with cases.…”