Selection of diverse strains to assess broad coverage of the bivalent FHbp meningococcal B vaccine

MenB-FHbp is a recombinant meningococcal serogroup B (MenB) vaccine composed of 2 factor H binding proteins (FHbps). Meningococcal vaccines targeting polysaccharide serogroup A, C, Y, and W capsules were licensed upon confirmation of bactericidal antibody induction after initial efficacy studies with serogroup A and C vaccines. Unlike meningococcal polysaccharide vaccines, wherein single strains demonstrated bactericidal antibodies per serogroup for each vaccine, MenB-FHbp required a more robust approach to demonstrate that bactericidal antibody induction could kill strains with diverse FHbp sequences. Serum bactericidal assays using human complement were developed for 14 MenB strains, representing breadth of meningococcal FHbp diversity of ~80% of circulating MenB strains. This work represents an innovative approach to license a non-toxin protein vaccine with 2 antigens representing a single virulence factor by an immune correlate, and uniquely demonstrates that such a vaccine provides coverage across bacterial strains by inducing broadly protective antibodies. Neisseria meningitidis is an important cause of invasive meningococcal disease, effective vaccines exist for some serogroups but immunogenicity to the MenB group is poor. Thomas R. Jones and colleagues examine serum bactericidal responses from volunteers challenged with MenB-FHbp – a recombinant MenB vaccine containing two Factor H (FH)-binding proteins. Serum bactericidal responses are tested against 14 MenB clinical isolates selected in an unbiased manner to cover the vast breadth of FHbp antigen and epidemiological diversity. This work demonstrates the broad efficacy of the MenB-FHbp vaccine using a serum bactericidal activity as a surrogate of protection.