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Vaccines based on multiple antigens often induce an immune response, which is higher than that triggered by each single component, with antibodies acting cooperatively and synergistically in tackling the infection. An interesting example is the antibody response induced by the 4CMenB vaccine, currently licensed for the prevention of  Neisseria meningitidis  serogroup B (MenB). It contains four antigenic components: Factor H binding protein (fHbp), Neisseria adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), and Outer Membrane Vesicles (OMV). Monoclonal and polyclonal antibodies raised by vaccination with 4CMenB show synergistic activity in complement-dependent bacterial killing. This review summarizes published and unpublished data and provides evidence of the added value of multicomponent vaccines. The ability of 4CMenB vaccine to elicit antibodies targeting multiple surface-exposed antigens is corroborated by the recent data on real-world evidences. Bactericidal activity is generally mediated by antibodies that bind to antigens highly expressed on the bacterial surface and immunologically related. However, simultaneous binding of antibodies to various surface-exposed antigens can overcome the threshold density of antigen–antibody complexes needed for complement activation. The data discussed in this review highlight the interplay between antibodies targeting major and minor antigens and their effect on functionality. www.clinicaltrials.gov  identifiers of studies with original data mentioned in the article: NCT00937521, NCT00433914, NCT02140762, and NCT02285777.

Synergistic activity of antibodies in the multicomponent 4CMenB vaccine