Correlates of protection for meningococcal surface protein vaccines: lessons from the past

Figures & data

Table 1. Numbers and percentages of sera showing hSBA titers ≥1:4 and ≥1:8 against the different meningococcal strains before and after hexavalent OMV vaccination [77]

Bleed	hSBA titer cutoff	hSBA target strain (PorA)
		M00 242,966 (P1.19,15–1)^a	M00 243,286 (P1.19–1,15–14)	M00 242,768 (P1.19–1,15–13)	M00 243,089 (P1.19–12,15–11)	M01 241,666 (P1.19–4,15)
Prevaccination	≥1:4	8 (28%)	2 (12%)	4 (14%)	0 (0%)	14 (49%)
	≥1:8	4 (14%)	1 (6%)	0 (0%)	0 (0%)	6 (21%)
Postvaccination	≥1:4	24 (92%)	12 (92%)	14 (70%)	12 (63%)	22 (88%)
	≥1:8	23 (88%)	12 (92%)	5 (25%)	7 (37%)	20 (80%)

hSBA = serum bactericidal antibody using human complement; MenB = meningococcal serogroup B; OMV = outer membrane vesicle; PorA = porin A.

^aMatches the vaccine.

Table 2. Effect of different calculation methods on the percentages of individuals (>18 years of age) achieving ≥4-fold rises in hSBA titer from baseline to postvaccination with MenBvac [70]

hSBA target strain	Percentages with ≥4-fold rise in hSBA titer
	Calculation method 1^a	Calculation method 2^b
44/76-SL	75.0	62.5
NZ 98/254	52.2	34.8
M01 240,013	34.8	34.8
M01 240,101	17.4	8.7
M01 240,149	26.1	17.4
M01 240,185	17.4	17.4
M01 240,355	34.8	34.8

hSBA = serum bactericidal antibody using human complement; MenBvac = Norwegian outer membrane vesicle vaccine.

^aIncludes all individuals with ≥4-fold rises in hSBA titer (including individuals with a baseline titer of <1:2 achieving a titer of ≥1:4 after the third dose of MenBvac).

^bOnly includes individuals with ≥4-fold rises in hSBA titer and a titer ≥1:8 after the third dose of MenBvac (i.e., for individuals with a baseline titer of <1:2, a titer of ≥1:8 had to be attained after the third dose of MenBvac).

Table 3. Known diversity of major surface-expressed meningococcal proteins, including those used in current surface protein vaccines [34,100–102]

Protein/antigen	Alleles, n^a
PorA VR2	988
FHbp	1728
NHBA (NEIS2109)	1706
NadA (NEIS1969)	314

FHbp = factor H binding protein; NadA = Neisserial adhesin A; NHBA = Neisseria heparin-binding antigen; PorA = porin A; VR = variable region.

^aAs of October 2020 (https://pubmlst.org/).

Table 4. Individuals (>18 years of age) showing ≥4-fold rises in hSBA titer from before to after MenBvac administration against different serogroup B target strains [70]

hSBA target strain	Phenotype	Sequence type	Clonal complex	≥4-fold rise in hSBA titer, n/N (%)^a
Homologous vaccine strain
44/76-SL	B:15:P1.7,16	32	32	18/24 (75)
Heterologous strains
NZ 98/254	B:4:P1.7–2,4	42	41/44	12/23 (52.2)
M01 240,013	B:NT:P1.22,9	275	269	8/23 (34.8)
M01 240,101	B:NT:P1.19–1,15–11	1049	269	4/23 (17.4)
M01 240,149	B:4:P1.7–2,4	41	41/44	6/23 (26.1)
M01 240,185	B:2a:P1.5–1,10–8	11	11	4/23 (17.4)
M01 240,355	B:1:P1.22,14	213	213	8/23 (34.8)

hSBA = serum bactericidal antibody using human complement; MenBvac = Norwegian outer membrane vesicle vaccine.

^aIndividuals with ≥4-fold rises in hSBA titer from before to after third dose of MenBvac.

Findlow J, Lowe A, Deane S, et al. Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine in toddlers and school children. Vaccine. 2005 Apr 8;23(20):2623–2627.

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