What is this project about?
One of the protective components of new MenB vaccines is a protein called fHbp – infants vaccinated with MenB vaccines produce antibodies against this protein, so that if they are exposed to MenB infection, these antibodies will kill the bacteria. However, some MenB strains do not have high levels of fHbp on their surface, so protection against these bacteria has to come about through the presence of other proteins in the vaccine.
In this project, scientists aim to develop a test for directly quantifying how much fHbp is present on a particular meningococcal strain, even if samples of blood or spinal fluid taken from a patient do not contain enough viable bacteria to culture them for identification.
If someone has been vaccinated against MenB, but still gets disease, this test could be used to evaluate whether the strain that caused disease has enough fHbp to be covered by the vaccine.
Why is this important?
The Bexsero® vaccine will provide protection against most (73-88%) but not all of the MenB strains that cause disease in the UK. This means that there may be cases of disease in people who have been vaccinated with Bexsero®. It will be very important to determine whether these disease cases are due to strains that are NOT covered by the vaccine or by strains that should be covered by the vaccine as this information will indicate how well the vaccine is working. Our current tests use ‘live’ bacteria for determining whether strains are covered by the vaccine. However, we are unable to isolate the causative strain from many disease cases often because antibiotic treatment has killed the infecting strain. There is therefore a need for tests that can measure the amount of the vaccine antigens directly in blood and spinal fluid samples from patients. Our research aims at developing a test of this type.
Two approaches will be taken:
- Assessing DNA signals in clinical samples. DNA contains the code for making the fHbp protein and the team will look to measure signals in this DNA that correlate with how much fHbp is produced.
- Assessing RNA signals in clinical samples. RNA is the intermediary between the DNA code and the constructed protein. The research team will measure RNA signals to see if this also correlates with fHbp production.
If feasibility is established, we anticipate that the test could be used immediately for assessing vaccine coverage in a small number of cases and that a full diagnostic test could be made available to Public Health England, potentially covering the introduction of a new MenB vaccine to the childhood schedule.