Using the HBP1 protein to make a new meningococcal vaccine
Professor Jon Sayers, University of Sheffield
Professor Jon Sayers and his team will be exploring whether the HBP1 protein could be used in a vaccine to protect against meningococcal meningitis.
In order to cause serious disease, normal meningococcal bacteria need to be able to migrate from the surfaces of the throat and penetrate into the blood stream. Once in the bloodstream the only available sources of the essential nutrient iron are in the form of haem and haemoglobin.
Professor Sayers and his team have identified an interesting protein that is produced by the bacterium that causes meningococcal meningitis and septicaemia. The protein allows the bacterium to use components of human blood (haem or haemoglobin) as a source of the essential nutrient iron. Test-tube-based experiments indicate that without the protein these bacteria cannot grow on either haem or haemoglobin.
In a preliminary experiment, the team raised antibodies against the meningococcal protein (HBP1) and found that these antibodies were able to guide the human immune system to attack and kill the bacteria. This raises the possibility that this meningococcal protein might be useful as a vaccine against meningococcal disease
The aim of this project is to examine the potential of the HBP1 protein in raising a useful antibody response.
The use of the HBP1 protein in vaccine design could lead to more effective vaccines to protect against meningococcal meningitis (including Meningitis B).
This project is due to start in June 2012.
Outcomes will be shown here once the project is complete.
Using the HBP1 protein as a candidate vaccine for meningococcal disease
Professor Jon Sayers, University of Sheffield
Professor Jon Sayers and his team will be exploring whether the HBP1 protein could be used in a vaccine to protect against meningococcal meningitis.
In order for the pathogenic Neisseriae to cause systemic disease, they first spread from the nasopharynx of the infected individual by invading the surrounding tissue and the bloodstream. Once the bacteria enter the bloodstream, haem and haemoglobin become their main source of iron, an essential nutrient for survival.
Professor Sayers and his team have studied a previously uncharacterised secreted neisserial protein that is able to bind haem in vitro. They have named this protein HBP1. The team inactivated the gene encoding this protein in a serogroup B N. meningitidis (MC58) isolate. This knockout (MC58∆hbp1) and the parent MC58 were able to grow on rich media and in defined culture conditions with iron sulphate as ferrous sulphate as sole iron source. MC58 also grew on haemor haemoglobin as the only source of iron but crucially, the knockout failed to grow in these conditions. They were also able to express and purify an insoluble form of HBP1 which was used in a pilot study to raise antibodies. The antibodies generated showed some activity in a serum bactericidal assay against MC58 suggesting that this proteins could be a potential vaccine candidate.
The aims of this project are to determine whether HBP1 antisera raised against soluble forms of the antigen are able to direct complement-mediated killing of a range of neisserial isolates and to explore the genetic variability of the gene encoding this protein.
This project is due to start in June 2012.
Outcomes will be shown here once the project is complete.
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