The use of vitronectin binding regions of meningococcal surface proteins Msf and Opc in vaccine design.
Meningococcal bacteria are a common cause of meningitis and septicaemia. Five groups of these bacteria cause most of the disease (A, B, C, W and Y) and well established vaccines exist for A, C, W and Y. It has been difficult to develop a vaccine against MenB but in 2015 a new MenB vaccine was introduced to the UK vaccination programme.
This is a huge breakthrough in the fight against this disease but unfortunately the vaccine is not predicted to protect against all MenB bacteria that cause disease. These non-vaccine preventable strains are likely to continue causing death and disability and there is therefore an urgent need to develop vaccines which prevent infection caused by all meningococcal bacteria.
What the research team did
Previous research has shown that these bacteria have a number of proteins on their surface, which appear to increase their ability to avoid being killed by our natural defences. One way in which this may occur is by the bacteria binding to our own molecules, which normally stop our defences damaging our own bodies. Some bacterial proteins which do this are already showing promise as part of a vaccine against meningococcal bacteria. The researchers have identified the interaction of two meningococcal proteins (Msf and Opc) with a human defence inhibitor protein (vitronectin). Their main aim is to test if the parts of the bacterial proteins which bind to human vitronectin create an immune response that will kill meningococcal bacteria. These regions will be tested for their suitability as part of a vaccine against the different groups of bacteria.
Vaccines are the only way to protect people from the devastation of meningococcal meningitis and septicaemia. While amazing progress has been made, there is still no vaccine that can protect against all meningococcal bacteria. If Professor Virji and her team are successful this research will take us one step closer to a vaccine that would completely protect the UK from this disease.
Summary and impact of results
This research has provided evidence that the vitronectin binding regions of both Msf and Opc proteins are able to stimulate the production of antibodies that not only kill meningococcal bacteria, but also block the binding of the bacterial proteins to human vitronectin.
Data from the project predicts that a vaccine containing both Msf and Opc proteins could protect against approximately 97% of meningococcal isolates. The inclusion of the Msf protein is particularly significant as it could lead to a vaccine that not only protects against invasive disease, but also has an impact on meningococcal carriage.
Further studies are now needed to determine the effectiveness of a vaccine containing a combination of these proteins. These studies need to include different routes for vaccine delivery, and whether the proteins can be added to existing vaccines, such as Bexsero® to increase protection against meningococcal disease.
Ultimately, these proteins could form part of an improved vaccine that could protect against all meningococcal disease.
Identification and therapeutic potential of a vitronectin binding region of meningococcal Msf. Hill DJ, Griffiths NJ, Borodina E, Andreae CA, Sessions RB, Virji M. PLoS One, 2015 Mar 31;10(3):e0124133. doi: 10.1371/journal.pone.0124133.