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. In the case of meningococcal vaccines, 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. 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. The interplay between antibodies targeting major and minor antigens and the effect on functionality provides the evidence of the added value of multicomponent vaccines.