MenDeVAR (Meningococcal Deduced Vaccine Antigen Reactivity) Index

Protein-based meningococcal vaccines contain surface proteins as vaccine antigens. These proteins demonstrate nucleotide and amino acid sequence diversity.

The Deduced Vaccine Antigen Reactivity (MenDeVAR) Index was developed to combine multiple, complex data that inform the reactivity of the Bexsero® and Trumenba® vaccines against specific antigenic variants.

  • Bexsero® (4CMenB) is a multicomponent vaccine. Peptide sequence diversity can be analysed using the Bexsero Antigen Sequence Typing (BAST) scheme (Brehony et al. 2016). The vaccine contains antigen variants: fHbp peptide 1; NHBA peptide 2; NadA peptide 8; PorA VR2 4.
  • Trumenba® (rLP2086) is a bivalent fHbp-containing vaccine. Peptide sequence diversity can be analysed using the fHbp peptide locus. The vaccine contains fHbp peptide variants 45 and 55.

MenDeVAR is described in Rodrigues et al. 2020, J Clin Microbiol 59(1):e02161-20. Please contact us if you have queries.

The MenDeVAR web application

Launch MenDeVAR

Upload a meningococcal genome assembly by pasting in to the web form or uploading a FASTA file. On submission, the protein variants found in the genome are determined and the vaccine reactivity results given as below for each vaccine:

  • exact match: isolate contains ≥1 exact sequence match to antigenic variants found in the vaccine.
  • cross-reactive: isolate contains ≥1 antigenic variant deemed cross-reactive to vaccine variants through experimental studies.
  • none: all the isolate's antigenic variants have been deemed not cross-reactive to vaccine variants through experimental studies.
  • insufficient data: isolate contains antigens for which there is insufficient data from or are yet to be tested in experimental studies.

The output is supplemented with a detailed description of the evidence supporting the result. Only evidence published in the scientific literature is used.

Caveats

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) assay was used for Bexsero®. The meningococcal antigen surface expression (MEASURE, McNeil et al. 2018) 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.

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 development, Bexsero® vaccine recipients were infants who had received 3 doses of vaccine and then a booster at 12 months (Donnelly et al. 2010). The pooled sera used for the MATS assay were taken from the toddlers at 13 months of age. For Trumenba® ,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.