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, bioRxiv 2020.08.18.256834. 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, bioRxiv 2020.08.18.256834. Please contact us if you have queries.
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