The MenDeVAR Index

This post discusses research carried out by our lab into the use of different vaccines against the bacterial species Neisseria meningitidis, which causes bacterial meningitis. You can read the full scientific paper, “Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: A Rapid and Accessible Tool That Exploits Genomic Data in Public Health and Clinical Microbiology Applications” (Rodrigues, et al., 2020), here.

Group B Meningococcus  

Bacterial meningitis is a serious infection of the protective membranes surrounding the brain and spinal cord. It can be caused by several species of bacteria including Neisseria meningitidis (the meningococcus). Meningococcal infections are generally sporadic – they occur infrequently as isolated cases – however outbreaks can occur where lots of people are living or working alongside one another, such as schools, universities, or military barracks.

The meningococcus can be divided into subtypes, known as serogroups, the most common of which is Group B (often referred to as MenB). Group B is currently the main cause of severe meningococcal disease outbreaks in Europe and North America¹.

Vaccinating against MenB

Since 2014/15, two vaccines have been used to protect against disease caused by MenB:

• Trumenba^® – manufactured by Pfizer
• Bexsero^® (sometimes called 4CMenB) – manufactured by GlaxoSmithKline

The Trumenba and Bexsero vaccines both contain proteins found on the surface of MenB bacteria. They work by ‘training’ the immune system to recognise these proteins, so that if a MenB cell invades it can be quickly identified and destroyed.

The vaccine proteins can be:

• An exact match – the sequence of the protein in the vaccine is exactly the same as the sequence of the protein on the surface of the MenB cell
• Cross-reactive – the vaccine protein sequence is slightly different to the MenB cell surface protein sequence, but similar enough that the cell will still be recognised by the immune system following vaccination  

The two vaccines contain a slightly different collection of proteins, meaning one may be more effective than the other against a given variant of MenB.

When outbreaks of meningococcal disease occur in a community, the spread of disease can be minimised by rapidly vaccinating those at risk. To make decisions about which vaccine to use, information is needed about:

• The sequence of surface proteins present on the MenB variant causing the outbreak
• Which vaccine will best train the immune system to recognise these proteins

This information can be worked out using laboratory techniques, but lab methods are often too slow to use in real-time clinical settings. This is where genomics comes in!

If tested in the lab, it takes several days to work out whether each vaccine is an exact match, cross-reactive, or ineffective against a MenB strain, due to the time it takes for bacterial samples to grow in test tubes. If this information is instead predicted from genomic data, results can be obtained within minutes.

The MenDeVAR Index

The MenDeVAR (Meningococcal Deduced Vaccine Antigen Reactivity) Index is a tool that uses genomic data to determine which vaccine to use against a given MenB variant². It was created by Rodrigues and colleagues in 2020 and is available to use as part of the PubMLST database. PubMLST is an online database of bacterial genomes, associated data such as where the genomes were collected, and analysis tools including MenDeVAR.

The MenDeVAR tool predicts which vaccine, Trumenba or Bexsero, will work best against an outbreak of meningococcal disease based on genomic data obtained from the outbreak MenB variant.

The tool works as follows:

• A sample of bacteria is collected from the patient with meningococcal disease, and the bacterial genome (the DNA) is sequenced
• The genome sequence from the MenB variant is uploaded to PubMLST
• The amino acid sequences of the surface proteins coded for by the DNA are determined
• These protein sequences are compared to the sequences of the proteins that each vaccine contains
• The tool works out if the MenB and vaccine sequences:
  • Are an exact match
  • Are cross-reactive (using experimental evidence that has been published in scientific papers)
  • Will not be cross-reactive (i.e., the vaccine will not work)
  • Or determines if there is not enough data to make a prediction
• The outputs are displayed using a ‘traffic light’ system so it is easy to see the prediction for each vaccine

An exact match is best, because this means the immune system will be trained by the vaccine using exactly the same protein as is found on the outbreak MenB variant. A result of cross-reactive also means the immune system would be trained to produce a successful response if this vaccine was used. However, the response may be less efficient than if an ‘exact match’ vaccine was used. This is because being cross-reactive means the vaccine protein is slightly different to the MenB protein, instead of matching it exactly.

If an exact match is found, the exact match vaccine will be recommended for use during an outbreak. If an exact match is found for both vaccines, then both will be recommended. Where there is no exact match but one of the vaccines is found to be cross-reactive, then this vaccine is recommended. If both vaccines are cross-reactive, then both are likely to be effective and both will be recommended.