The important lessons lurking in the history of meningococcal epidemiology

Figures & data

Figure 1. Cross-sectional diagram of the meningococcal cell envelope and capsule [1], with an insert highlighting fHbp as an example of the production, transport, and cellular expression of outer membrane proteins [18]. fHbp=factor H binding protein. Main figure is adapted with permission from Rosenstein NE et al. N Engl J Med. 2001;344:1378–1388 [1]. Inset is adapted under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) from da Silva RAG et al. Front Microbiol. 2019;10:2847 [18].

Table 1. Meningococcal vaccine classes and their attributes.

	Attributes					References
Serogroup Vaccine class	Cross-reactivity	Persistence	Immunologic memory	Acquisition and carriage	Other
A, C, W, Y
Plain polysaccharide	Protect against all strains within the corresponding serogroup(s)	Relatively short persistence of protective antibodies, necessitating dosing every 3−5 years; however, repeated dosing may lead to immune hyporesponsiveness	Induce a T-cell–independent response that is not associated with immunologic memory	Not thought to reduce meningococcal acquisition and carriage	Safe and immunogenic in older children and adults, but generally poorly immunogenic (and therefore anticipated to be ineffective) in the very young	[13,56–58]
Polysaccharide conjugate*^†	Protect against all strains within the corresponding serogroup(s)	Persistence of antibody levels generally demonstrated over multiple years	Induce a T-cell–dependent response that is associated with immunologic memory	Reduce meningococcal acquisition and carriage	Immunogenic in all ages, including infants	[14,56–64]
B
Outer membrane vesicle	Protect predominantly against the strain used to produce the vaccine but not against other diverse MenB strains	Protective antibody levels and effectiveness show substantial waning within months after primary series, particularly in infants	Booster dosing induces anamnestic immune responses, indicative of immunologic memory	Mixed findings regarding effects on meningococcal acquisition and carriage		[13,57,65,66]
Subcapsular protein-based^†‡	Intended to provide broad protection against MenB disease, with protection against a given strain depending on the strain’s susceptibility to vaccine-induced antibodies	Antibody levels show waning within ≥12 months after primary vaccination series, depending on test strain	Booster dosing induces anamnestic immune responses, indicative of immunologic memory	Do not reduce meningococcal acquisition and carriage		[58,67–71]

fHbp=factor H binding protein; MenABCWY=meningococcal serogroups A, B, C, W, and Y; MenACWXY=meningococcal serogroups A, C, W, X, and Y; MenACWY=meningococcal serogroups A, C, W, and Y; MenB=meningococcal serogroup B; MenB-4C=4-component MenB vaccine; MenB-fHbp=bivalent fHbp MenB vaccine.

*A MenACWXY vaccine that received prequalification from the World Health Organization in July 2023 [72] is also formulated using polysaccharide conjugates from serogroups A, C, W, X, and Y [73,74].

^†MenABCWY vaccines, one of which received US licensure in October 2023 [75] and another of which remains investigational [61,76,77], are both based on licensed MenACWY polysaccharide conjugate and MenB subcapsular protein-based vaccines.

^‡The 2 currently approved serogroup B subcapsular protein-based vaccines differ in antigenic composition: MenB-4C includes single variants of each of 3 surface-exposed antigens (nonlipidated fHbp [variant B24/1.1], Neisseria adhesin A, and Neisserial heparin binding antigen), as well as outer membrane vesicles, whereas MenB-fHbp includes 2 lipidated fHbp variants, 1 from each subfamily (A05/3.45 and B01/1.55) [58,61].

Figure 2. Number of cases of meningococcal disease during 1912 to 1998 in England and Wales and 1999 to 2021 in England. Sections indicate reporting terms during different periods. Adapted under the terms of the Creative Commons Attribution-Non Commercial license (https://creativecommons.org/licenses/by-nc/3.0/) from Christensen H et al. BMJ. 2014;349:g5725 [92]. Data from 1912 to 1998 are from Ramsay M. Use of MLST in the epidemiology of meningococci (https://webarchive.Nationalarchives.gov.uk/ukgwa/20140714074352/http://www.Hpa.org.uk/webc/hpawebfile/hpaweb_c/1194947392421) [91]. Data from 1999 through 2021 are from UK Health Security Agency. Laboratory confirmed cases of invasive meningococcal infection in England: annual report for 2021 to 2022 supplementary data tables (https://www.Gov.uk/government/publications/meningococcal-disease-laboratory-confirmed-cases-in-england-in-2021-to-2022) [81], with 1998/1999 data used for 1999, 1999/2000 data used for 2000, etc.

Figure 3. IMD percentage serogroup distribution across worldwide regions in recent years. IMD=invasive meningococcal disease; NG=nongroupable. *Serogroup A is included in the “other” category. ^†Serogroups other than B, C, W, and Y are included in the NG category. ^‡Specific countries include Benin, Burkina Faso, Cameroon, Central African Republic, Ghana, Mali, Niger, Nigeria, Senegal, South Sudan, Chad, and Togo. Reproduced under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) from Pardo de Santayana C et al. Epidemiol Infect. 2023;151:e57 [9].

Figure 4. Countries with recent MenACWY vaccine recommendations. MenACWY=meningococcal serogroups A, C, W, and Y. *In all provinces apart from Quebec. ^†Hawaii (United States), Malta, and Cyprus are not shown to scale or to shape. Adapted under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives license (https://creativecommons.org/licenses/by-nc-nd/4.0/) from Serra L et al. Hum Vaccin Immunother. 2021;17:2205–2215 [102]. Additional data from MacNeil JR et al. Clin Infect Dis. 2018;66:1276–1281 [99]; Koliou M et al. Euro Surveill. 2020;25:1900534 [111]; and Badur S et al. Infect Dis Ther. 2021;10:2035–2049 [115].

Figure 5. Current routine meningococcal vaccination recommendations across select countries [106,135–142]. ACWY=meningococcal serogroups A, C, W, and Y; B=meningococcal serogroup B; C=meningococcal serogroup C. *Catch-up vaccination. ^†Based on shared clinical decision-making. ^‡Depending on local epidemiology and programmatic considerations.

Table

AMR	Antimicrobial resistance
cc11	Clonal complex 11
CFR	Case-fatality rate
cps	Capsule polysaccharide synthesis gene
CSF	Cerebrospinal fluid
fHbp	Factor H binding protein
IMD	Invasive meningococcal disease
LOS	Lipooligosaccharide
MCC	Meningococcal serogroup C polysaccharide conjugate vaccine
MenA	Meningococcal serogroup A
MenA-TT	Meningococcal serogroup A polysaccharide tetanus toxoid conjugate vaccine
MenABCWY	Meningococcal serogroups A, B, C, W, and Y vaccine
MenACWXY	Meningococcal serogroups A, C, W, X, and Y vaccine
MenACWY	Meningococcal serogroups A, C, W, and Y
MenACWY-CRM197	Meningococcal serogroups A, C, W, and Y polysaccharide CRM197 conjugate vaccine
MenACWY-D	Meningococcal serogroups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine
MenACWY-TT	Meningococcal serogroups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine
MenACYW-TT	Meningococcal serogroups A, C, Y, and W polysaccharide tetanus toxoid conjugate vaccine
MenB	Meningococcal serogroup B
MenB-4C	4-component MenB vaccine
MenB-fHbp	Bivalent fHbp MenB vaccine
MenC	Meningococcal serogroup C
MenW	Meningococcal serogroup W
MenX	Meningococcal serogroup X
MenY	Meningococcal serogroup Y
MLEE	Multilocus enzyme electrophoresis
MLST	Multilocus sequence typing
MSM	Men who have sex with men
NG	Nongroupable
NIP	National immunization program
OMV	Outer membrane vesicle
PCR	Polymerase chain reaction
PorA	Porin A
PorB	Porin B
ST	Sequence type
WGS	Whole-genome sequencing
WHO	World Health Organization

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