A universal vaccine for serogroup B meningococcus

Abstract

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.meningococcus B ͉ reverse vaccinology

Hospital-based surveillance of meningococcal meningitis in Salvador, Brazil

“…However, existing limitations of OMV-based meningococcal vaccines, including lower efficacy in young children (Costa et al, 1996;De Moraes et al, 1992;Sierra et al, 1991;Tappero et al, 1999), inability to induce immunological memory (Wedege et al, 1998) and failure to provide cross-protection against non-vaccine strains, may delay their use (Pollard and Levin, 2000). Alternatively, reverse vaccinology approaches have identified antigens that induce antibactericidal antibody responses against the spectrum of meningococcal serogroup B strains associated with invasive disease (Giuliani et al, 2006;Masignani et al, 2003). These target antigens are being evaluated as candidates for a universal serogroup B subunit vaccine and, if effective, will be an important intervention against this disease in epidemiological situations such as encountered in Brazil.…”

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

“…18,19 4CMenB consists of 4 components, including 3 recombinant proteins that were identified by genome mining as surface antigens common to many serogroup B strains, factor H-binding protein (fHbp), Neisseria adhesin A (NadA) and Neisserial Heparin Binding Antigen (NHBA) (the latter 2 antigens are included as fusion proteins with other Neisseria proteins), combined with outer membrane vesicle (OMV) components from the New Zealand outbreak strain NZ98/254. [19][20][21][22] Results from Phase 2 and 3 clinical studies demonstrated that 4CMenB elicited strong bactericidal responses against the vaccine antigens and was generally well tolerated when used in infants and children, adolescents and adults. [21][22][23][24][25][26] 4CMenB has been approved in the EU, Australia, Canada, Chile, and Uruguay for use in individuals beginning from 2 months of age and in the US for use in individuals 10 to 25 y of age.…”

Men B: lack of coverage or vaccine failure?

“…Bexsero® comprises three recombinant proteins (fHbp, NHBA and NadA) and detergent-extracted outer membrane vesicles containing native PorA protein and several minor proteins. 2 The recombinant proteins exhibit significant diversity in both sequence and levels of expression between meningococcal strains, so that protection only occurs if a strain has mediumto-high expression of one or more homologous antigens. Monitoring requires detection of whether antigens have the requisite homology and expression to render an infective strain sensitive to protection by Bexsero®.…”