Meningococcal B vaccine (4CMenB): the journey from research to real world experience

Figures & data

Table 1. Antigen components of 4CMenB and rLP2086 and rationale for their selection.

Vaccine	Antigen	Sequence variant	Rationale
4CMenB	50 µg fHbp fused to accessory protein GNA2091	fHbp (Family B) Variant 1.1	Recombinant fHbp induced SBA against a broad range of variant 1 strains and passive protection against homologous and heterologous meningococcal challenge in animal models [74]. GNA 2091 is an accessory antigen shown to convey protection in animal models [4].
	50 µg NHBA fused to accessory protein GNA 1030	NHBA Peptide 2	NHBA induces SBA against strains carrying different peptides [75], and antibodies against NHBA are protective in animal models against homologous and heterologous N. meningitidis strains [76]. Antibodies to fHbp, OMV and NHBA also work synergistically to induce SBA [22]. GNA 1030 is an accessory antigen that induces bactericidal antibodies and conveys protection in animal models [4].
	50 µg NadA	Variant 3	NadA is highly immunogenic and induces cross-reactive SBA responses against strains carrying the nadA gene [77,78] Anti-NadA-specific antibodies in sera from immunized infants passively protected infant rats by bacteremia in a challenge model [79].
	25 µg OMV	NZ98/254 PorA 1.4	OMV is highly effective in inducing SBA and is the same OMV used to curtail a MenB epidemic in New Zealand [7]. Inclusion of the OMV component induced a specific protective response against P1.4 homologous strains [6], and improved immunogenicity against heterologous strains by contributing with minor antigens
rLP2086	60 µg fHbp	A05 (Variant 3.45)	Recombinant lipidated fHbp induced SBA against a strains expressing a threshold level of fHbp, and passive protection against homologous and heterologous meningococcal challenge in animal models [74]. A combination of two genetically different fHbp subfamilies induces strain coverage dependent on fHbp sequence diversity and expression level
	60 µg fHbp	B01 (Variant 1.55)

fHbp = factor H binding protein, GNA = Genome-derived Neisseria Antigens, NadA = Neisseria adhesin A, NHBA = Neisserial Heparin Binding Antigen, OMV = outer membrane vesicle, PorA = porin A, SBA = serum bactericidal antibodies, IMD = invasive meningococcal disease, MenB = meningococcus serogroup B

Figure 1. 4CMenB: the journey from early research to real world experience.

MATS = Meningococcal Antigen Typing System, hSBA = serum bactericidal antibodies using human complement, IMD = invasive meningococcal disease. Figure references: 1 = [26], 2 = [80], 3 = [81], 4 = [14].

Figure 2. Focus on the patient section.

Figure 3. Synergy of C1q engagement by (a) monoclonal antibodies binding to two different antigens on the bacterial surface or (b) two monoclonal antibodies binding to the same antigen.

Figure 4. Effect of alternate vaccination strategies on annual disease cases.

VEC = vaccine efficacy against carriage, SC = strain coverage, CU = one-off catch up vaccination. Routine vaccination infant at 2, 3, 4, and 12 months of age (blue line) and adolescent vaccination at age 13 years (2 doses) (dashed yellow line). Combined strategy refers to routine vaccination infant at 2, 3, 4, and 12 months (3 + 1 doses) and adolescent at 13 years (2 doses). This could be switched after 10 years to routine infant at 2, 4, and 12 months (2 + 1 doses) and adolescent at 13 years (2 doses) (dashed green line). Reproduced from [60]: "Re-evaluating cost effectiveness of universal meningitis vaccination (Bexsero) in England: modelling study." Hannah Christensen, Caroline L Trotter, Matthew Hickman, W John Edmunds, 2014;349:g5725. With permission from BMJ Publishing Group Ltd.

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