Bexsero® (4CMenB) is a multicomponent vaccine.
- Protein-based meningococcal vaccines contain surface proteins as vaccine antigens, these proteins demonstrate nucleotide and amino acid sequence diversity.
- Peptide sequence diversity can be analysed using the Bexsero Antigen Sequence Typing (BAST) scheme1.
- Bexsero® contains: fHbp peptide 1; NHBA peptide 2; NadA peptide 8; PorA VR2 4.
The Deduced Vaccine Antigen Reactivity (MenDeVAR) Index was developed to combine multiple, complex data that inform the reactivity of each vaccine against specific antigenic variants.
The MenDeVAR Index:
- isolate contains ≥1 exact sequence match to antigenic variants found in the vaccine.
- isolate contains ≥1 antigenic variant deemed cross-reactive to vaccine variants through experimental studies.
- all the isolate's antigenic variants have been deemed not cross-reactive to vaccine variants through experimental studies.
- isolate contains antigens for which there is insufficient data from or are yet to be tested in experimental studies.
It is important to understand the caveats to interpreting the MenDeVAR Index:
Source of data - These data combine multiple sources of information including: peptide sequence identity through whole genome sequencing; experimental assays developed as indirect measures of the breadth of vaccine protection against diverse meningococci; and assays developed to assess immunogenicity. The Meningococcal Antigen Typing System (MATS)2 assay was used for Bexsero®.
Cross-reactivity definition - An antigenic variant was considered cross-reactive if it had been tested in ≥5 isolates/subjects and was above the accepted threshold in ≥75% of those isolates. This was established through combined analysis of published experimental studies (PMID provided for each variant), not from genomic data. These assays were based on serogroup B disease isolates.
Protein expression - We have not inferred from genomic data, therefore there may be isolates that possess genes but do no express the protein in vivo.
Age of vaccinees - For MATS assay development2, Bexsero® vaccine recipients were infants who had received 3 doses of vaccine and then a booster at 12 months. The pooled sera used for the MATS assay were taken from the toddlers at 13 months of age.
- Brehony C, Rodrigues CMC, Borrow R, et al. Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation. Vaccine 2016 34(39):4690-7
- Donnelly J, Medini D, Boccadifuoco G, et al. Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci USA 2010;107(45):19490-19495
MenDeVAR is described in Rodrigues et al. 2020, J Clin Microbiol 59(1):e02161-20. Please contact us if you have queries.
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Trumenba® (rLP2086) is a bivalent fHbp-containing vaccine.
- Protein-based meningococcal vaccines contain surface proteins as vaccine antigens, these proteins demonstrate nucleotide and amino acid sequence diversity.
- Peptide sequence diversity can be analysed using the fhbp peptide locus.
- Trumenba® vaccine contains fHbp peptides 45 and 551.
The Deduced Vaccine Antigen Reactivity (MenDeVAR) Index was developed to combine multiple, complex data that inform the reactivity of each vaccine against specific antigenic variants.
The MenDeVAR Index:
- isolate contains ≥1 exact sequence match to antigenic variants found in the vaccine.
- isolate contains ≥1 antigenic variant deemed cross-reactive to vaccine variants through experimental studies.
- all the isolate's antigenic variants have been deemed not cross-reactive to vaccine variants through experimental studies.
- isolate contains antigens for which there is insufficient data from or are yet to be tested in experimental studies.
It is important to understand the caveats to interpreting the MenDeVAR Index:
Source of data - These data combine multiple sources of information including: peptide sequence identity through whole genome sequencing; experimental assays developed as indirect measures of the breadth of vaccine protection against diverse meningococci; and assays developed to assess immunogenicity. The meningococcal antigen surface expression (MEASURE)2 and serum bactericidal activity (SBA) assays were used for Trumenba®.
Cross-reactivity definition - An antigenic variant was considered cross-reactive if it had been tested in ≥5 isolates/subjects and was above the accepted threshold in ≥75% of those isolates. This was established through combined analysis of published experimental studies (PMID provided for each variant), not from genomic data. These assays were based on serogroup B disease isolates.
Age of vaccinees - The age of vaccine recipients in the experimental studies varies widely, ranging from toddlers to adults, and needs to be taken into consideration when interpreting results. Vaccine studies used different schedules and doses of vaccines.
- Jiang HQ, Hoiseth SK, Harris SL, et al. Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease. Vaccine 2010;28(37):6086-93
- McNeil LK, Donald RGK, Gribenko A, et al. Predicting the Susceptibility of Meningococcal Serogroup B Isolates to Bactericidal Antibodies Elicited by Bivalent rLP2086, a Novel Prophylactic Vaccine. mBio 2018;9(2):e00036-18
MenDeVAR is described in Rodrigues et al. 2020, J Clin Microbiol 59(1):e02161-20. Please contact us if you have queries.
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Versions
More than one version of this isolate record exist.
- Older versions
- 344
Publications (10)
- Bennett JS, Jolley KA, Sparling PF, Saunders NJ, Hart CA, Feavers IM, Maiden MC (2007). Species status of Neisseria gonorrhoeae: evolutionary and epidemiological inferences from multilocus sequence typing. BMC Biol 5:35
- Bratcher HB, Corton C, Jolley KA, Parkhill J, Maiden MC (2014). A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of 108 representative Neisseria meningitidis genomes. BMC Genomics 15:1138
- Didelot X, Urwin R, Maiden MC, Falush D (2009). Genealogical typing of Neisseria meningitidis. Microbiology 155:3176-86
- Jolley KA, Sun L, Moxon ER, Maiden MC (2004). Dam inactivation in Neisseria meningitidis: prevalence among diverse hyperinvasive lineages. BMC Microbiol 4:34
- Jolley KA, Wilson DJ, Kriz P, McVean G, Maiden MC (2005). The influence of mutation, recombination, population history, and selection on patterns of genetic diversity in Neisseria meningitidis. Mol Biol Evol 22:562-9
- Lucidarme J, Lekshmi A, Parikh SR, Bray JE, Hill DM, Bratcher HB, Gray SJ, Carr AD, Jolley KA, Findlow J, Campbell H, Ladhani SN, Ramsay ME, Maiden MCJ, Borrow R (2017). Frequent capsule switching in 'ultra-virulent' meningococci - Are we ready for a serogroup B ST-11 complex outbreak? J Infect 75:95-103
- Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, Zhang Q, Zhou J, Zurth K, Caugant DA, Feavers IM, Achtman M, Spratt BG (1998). Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95:3140-5
- Thompson EA, Feavers IM, Maiden MC (2003). Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component. Microbiology 149:1849-58
- Urwin R, Russell JE, Thompson EA, Holmes EC, Feavers IM, Maiden MC (2004). Distribution of surface protein variants among hyperinvasive meningococci: implications for vaccine design. Infect Immun 72:5955-62
- Wang JF, Caugant DA, Morelli G, Koumaré B, Achtman M (1993). Antigenic and epidemiologic properties of the ET-37 complex of Neisseria meningitidis. J Infect Dis 167:1320-9
Sequence bin
- contigs
- 184
- total length
- 2,138,095 bp
- max length
- 110,296 bp
- mean length
- 11,621 bp
- N50
- 49,220
- L50
- 16
- N90
- 9,463
- L90
- 48
- N95
- 4,242
- L95
- 64
- %GC
- 51.72
- Ns
- 0
- gaps
- 0
- loci tagged
- 2,182
Show sequence bin
Annotation quality metrics
Provenance information
Missing field values for: age_range, disease, source
Scheme completion
Analysis
rMLST species identification
Analysis performed: 2022-11-29