Developing tools to assess Bexsero©

One on-going project at the University of Leicester is Dr Chris Bayliss' work to develop tools for assessing the effectiveness the Bexsero© vaccine. Very few vaccines are 100% effective so monitoring them is a key area of research. Before reading this page, you may want to read about the Bexsero© vaccine on the previous page.

The potential for vaccine failure makes the need to monitor Bexsero© all the more important. To help with the development of meningococcal vaccines, we should have an array of tools to determine whether a case of meningitis in a vaccinated individual has been caused by a strain we predict to be covered by the vaccine or not.

Scientists have observed massive differences in the amount of fHbp on the surface of infecting MenB cells. As differences in expression of fHbp can be a reason for vaccine failure, we are developing tools to measure the amount of fHbp expressed by infectious MenB and to identify DNA signatures that match to these different expression levels.

It is usually very difficult to isolate live MenB samples from patients with meningitis. This is because, as soon as meningitis is suspected, patients are given antibiotics killing the bacteria before we have chance to catch it. In this case, it can be very difficult to find anything out about the infecting strain, and whether we expected it to be covered by the vaccine.

To get around this, we are developing tests to type MenB cells directly from the sites of infection (blood etc). As fHbp provides the greatest source of uncertainty, this is the antigen we are focusing on. These techniques however may be adapted for use with different vaccine antigens in the future.

Bayliss Project

The current method for 'typing' MenB cells involves isolation of the organism from the site of infection, growth and analysis. The tools we're developing will directly analyse clinical samples such as blood or cerebral-spinal fluid (CSF).

To do this we are testing 3 different approaches

  • Firstly, we are attempting to measure levels of fHbp mRNA directly from clinical samples. mRNA is the intermediate code between DNA and protein. We think that the amount of mRNA present in a clinical sample may be a good indicator of how much fHbp was on the surface of each cell.

  • Secondly, we are looking to directly measure the amount of fHbp protein in the clinical samples. To do this we are going to use a method known as 'tandem mass spectroscopy'. We think that comparing the relationship between mRNA levels and protein levels in the blood may be the best way to find out whether or not failure of the vaccine was due to low fHbp levels on the bacterial cell.
  • Finally, we are investigating a way to group the promoters of fHbp genes from MenB cells expression different amounts of fHbp. Promoters are sequences of DNA before genes that determine how much of the gene will be expressed. If we can see that one promoter gives higher expression of fHbp than another, then we can compare this with the mRNA and protein levels from our other experiments to group promoters accordingly. From this, we may be able to directly tell how much fHbp a bacterium is expressing based on its promoter types alone.

fHbp

This three-pronged approach is helping us to develop a diagnostic tool for assessing vaccine efficacy.

This work is funded by the Meningitis Research Foundation. You can read more about their work and the other projects they fund on their website.

 

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