Product review on the IMD serogroup B vaccine Bexsero®

Figures & data

Table 1. Doses of 5CVMB in pre-clinical immunogenicity studies

Species	Treatment (route)	Dose of NHBA-953, 936-fHbp, and NadA each	Dose of OMV	Dose of Al(OH)3	Volume	Study no.
Mouse	Days 0, 21, 35 (IP^1)	20 µg	10 µg (NZ^4)	600 µg	200 µL	263903–01
Guinea pig	Days 0, 21, 35, 48 (SC^2)	25 µg	12.5 µg (NZ)	750 µg	250 µL
Juvenile baboon (9–20 months)	Day 0, months 1 + 2 (IM^3)	50 µg	25 µg (NW^5)	1.5 mg	0.5 mL	283886–01
Infant rhesus macaque (2–3 months)	Day 0, weeks 4 and 18 (IM)	50 µg	25 µg (NZ)	1.5 mg	0.5 mL	283887–01

¹Intraperitoneal; ²Subcutaneous; ³Intramuscular; ⁴New Zealand OMVs; ⁵Norwegian OMVs.

Table 2. Toxicity studies with different vaccine formulations

Study type	Treatment days	Dose of NHBA-953, 936-fHbp, and NadA each	Dose of OMV	Dose of Al(OH)3	Study no. (date)
Rabbit single and repeat-dose toxicity study	1, 15, 29, 43, 57	50 µg 100 µg	25 µg (NW^1/NZ^2) 25 µg (NW)	1.5 mg 3 mg	1228–102 (2005)
Rabbit reproductive + developmental toxicity (dose-finding)	Premating 1, 15, 29, GD^3 7, 20	50 µg 100 µg	25 µg (NZ) 50 µg (NZ)	1.5 mg 3 mg	UBA00041 (2008)
Rabbit reproductive + developmental toxicity (pivotal)	Premating 1, 15, 29, GD 7, 20	50 µg	25 µg (NZ)	1.5 mg	UBA00044 (2009)

¹Norwegian OMV; ²New Zealand OMV; ³Gestation day.

Table 3. Components of the Bexsero Vaccine

Component	Amount (per dose of 0.5 ml)	Relevant characteristics/function
FHbp (Factor H binding protein in fusion with the accessory protein GNA2091	50 µg	Negative regulatory protein of the alternative pathway of the complement
NHBA (Neisserial Heparin Binding Antigen in fusion with the accessory protein GNA1030	50 µg	Complement dependent Bacterial lysis
NadA (Neisserial Adhesin A	50 µg	Binding to epithelial cells
Vaccin OMV rMenB (strain NZ98/254, vaccin Men-ZB®)	25 µg	Mainly PorA outer membrane protein
Al(OH)3	1.5 mg	Adjuvant

Table 4. The major clinical studies for licensure

Study	Phase	Type	Population at enrollment	N° of arm(s) of the study*	N enrolled	Schedule (month)
V72P5	1	Observer blind, randomized single center	Adult 18–40y	1	28	0,1,2
V72P4	2	Open multicenter	Adult 18–50y	1	54	0,2,6
V72P6	2	Open multicenter randomized controlled	Infants 2 mo	2	50 24	2,4,6,12 12
V72P6E1	2	Open label single-center extension	Infants 2 mo, childfren 40 mo	3	19 8 43	2,4,6,12,40 12,40,42 40,42
V72P9	2	Single-blind, randomized, single-center	Infants (6–8mo)	1	30	6,8,12
V72P9E1	2	Open label single-center extension	Infants 6–8mo Childfen 40 mo Children 60 mo	3	14 41 49	6,8,12,40 40,42 60,62
V72P12	2	Open multicenter randomized	Infants 2 mo	3	627† 318† 628‡	2,4,6 2,3,4 2,4,6
V72P12E1	2	Open label multicenter extension	Toddlers 12, 18, 24 mo 4th booster dose at 12, 18 or 24 mo; 2 catch up doses at 12–14, 18–20 mo (naive) and in naive children (24–26 mo)	3	1588 246 51 + 56	Booster at 12, 18 or 24 months of age in subjects who received 3 doses of at 2,4,6 + Routine at 2,3,4 or 2,4,6 months in V72P12 at 12 and 14 months (in subjects who received routine at 2,3,4) at 18, 20 and at 24, 26 months of age
VP72P16	2	Partially observer-blind, randomized multicenter controlled	Infants (2mo)	8	Total 1507	2,3,4 8 vaccine groups injected with either different composition or formulation process of the meningococcal B antigens (groups I–VI), or with concomitant administration of paracetamol (Par+B+ OMV, group VIII), or receiving the control vaccine (MenC, group VII)
V72P10	3	Observer-blind multicenter randomized controlled	Adolescents (11–17y)	8	Total 1631	1 dose, or 2 doses [0,1 or 0,2], or 3 doses [0,1,2 or 0,2,6 or 0,1,6]
V72P13	3	Partially blinded randomized multicenter controlled	Infants (2mo)	3	Total 2481	2,4,6 Concomitant with routine Routine alone Routine+MenC
V72P13 E1	3	open label randomized multicenter extension	Toddlers (12 mo)	6	Total 2249	A booster 12 month for the groups of VP7213 (with MMRV) concomitantly or A mo aftewards
V72P13E2	3	Open label randomized multicenter extension	Toddlers 23 mo (naives)	3	Total 508 305 86 116	12mo persistence 3^rd dorse to 2-dose cach-up 2 doses in nive children 24mo and 26 mon

*Only the arms that used the final formulation (rMenB+OMVNZ) are mentioned in the Table.

† concomitant with routine vaccines, ‡ intercalated with routine vaccines at 3,5,7mo.

Table 5. Characteristics of the two protein-based vaccines targeting meningococci B

Vaccine	Bexsero®	Trumenba®
Composition	fHbp variant1 (subfamily B): 50 µg NHBA 50 µg NadA 50 µg PorA P1.4 25 µg	Lipidated proteines of:fHbp variant1 (subfamily B): 60 µg fHbp variant3 (subfamily AB): 60 µg
Licensure	Europe (EMA) (2013): ≥2 mo USA FDA (2015): ≥10 y	Europe (EMA) (20173): ≥10 y mo USA FDA (2015) ≥ 10 y
Schedule <10 y)	2 Mo-2y: 2 + 1 > 2 y-10y: 2 doses (0–2mo)	-
Schedule ≥ 10 y	> 10 y: 2 doses (0–1mo); booster unknown	2 doses (0–6mo) or 3 doses (0–1/2-6mo); booster unknown
Persistence of the immune response	Infants and toddlers 24–36 mo after booster Adolescents 4–7.5 years	4–5 y
Estimation of strain converge	78% (CI 63–90)	91% (71.5–99.3)*
Impact on acquisition of carriage	No	No
Protection against non-B isolates	Yes	Yes

*Range of coverage against reference strains.