Methods to evaluate the performance of a multicomponent meningococcal serogroup B vaccine

Abstract

Meningococcal serogroup B (MenB) vaccine licensure was based on the assessment of vaccine-induced immune responses by human serum bactericidal antibody (hSBA) assay against a small number of antigen-specific strains complemented by strain coverage predictions. However, the evaluation of vaccine strain coverage is challenging because of genotypic and phenotypic diversity in surface-exposed MenB strain antigens. This narrative review considers the principal methods applied to assess the performance of a multicomponent MenB vaccine at different stages of its development. Traditional hSBA assay against a limited panel of strains is useful at all stages, while predicted strain coverage methods, such as the meningococcal antigen typing system, are used independent of clinical trials. A new method, the endogenous complement hSBA assay, has been developed to evaluate a vaccine's ability to induce a bactericidal immune response in clinical trials, in conditions that approximate real-world settings through the use of each vaccinee's serum as a source of complement and by testing against a panel of 110 epidemiologically representative MenB strains. Each assay, therefore, has a different scope during the vaccine's development and all complement each other, enabling comprehensive evaluation of the performance of multicomponent MenB vaccines, in advance of real-world evidence of vaccine effectiveness and vaccine impact.

Keywords: 4CMenB; Neisseria meningitidis; invasive meningococcal disease; serum bactericidal antibody assay; vaccine; vaccine effectiveness.

Fig 1

Summary of methods to evaluate the performance of multicomponent meningococcal serogroup B (MenB) vaccines, i.e., vaccines that can elicit bactericidal antibodies against their different antigenic components.

Fig 2

Methods to predict meningococcal serogroup B (MenB) vaccine strain coverage: meningococcal antigen typing system (MATS) (24, 25), meningococcal antigen surface expression (MEASURE) assay (26), genetic MATS (gMATS) (27), meningococcal deduced vaccine antigen reactivity (MenDeVAR) index (28), and genomic coverage prediction (GeCoPred) (29). 4CMenB, 4-component meningococcal serogroup B vaccine; ELISA, enzyme-linked immunosorbent assay; fHbp, factor H binding protein; hSBA, human serum bactericidal antibody; IMD, invasive meningococcal disease; MenB-FHbp, bivalent factor H binding protein meningococcal serogroup B vaccine; NadA, Neisseria adhesin A; NHBA, neisserial heparin-binding antigen; PorA, porin A.

Fig 3

Comparable test-based breadth of immune response for investigational MenABCWY vaccine (0–6 months schedule) and 4CMenB vaccine (0–2, 0–6, and 0–2–6 months schedules), as shown by endogenous complement human serum bactericidal antibody assay against eight circulating strains from the 110 meningococcal serogroup B (MenB) strain panel that express porin A subtype P1.4 (PorA P1.4) (35). Strain M08785 has the same antigenic features as the PorA P1.4 indicator strain MenABCWY group, administered meningococcal serogroups ABCWY vaccine at months 0 and 6; 4CMenB 0–2 group, administered two doses of 4-component meningococcal serogroup B (4CMenB) vaccine at months 0 and 2; 4CMenB 0–6 group, administered two doses of 4CMenB at months 0 and 6; 4CMenB 0–2–6 group, administered three doses of 4CMenB at months 0, 2, and 6. CI, confidence interval.