Examination of two meningococcal surface proteins as potential vaccine targets
Current research
- University of Leicester, Leicester, UK
- Researchers:
Dr Christopher Bayliss, Dr Ed Kaczmarski, Dr Hannah Chan, Prof Ian Feavers
- Start Date: 01 July 2010
- Type: Scientific
Meningococcal septicaemia and meningitis due to serogroup B strains of
Neisseria meningitidis are significant causes of death and morbidity.
Protein-based vaccines are the major approach being taken to developing protection against serogroup B meningococcal disease but it is still unclear whether these vaccines will induce a long-lasting, broad-spectrum protective immune response.
Inclusion of minor outer membrane proteins in a multivalent vaccine may be required to increase the effectiveness of these prospective vaccines. Two phase-variable haemoglobin-binding receptors, HmbR and Hpu, are present in the outer membranes of meningococci. HmbR is associated with disease isolates while preliminary evidence indicates all disease isolates express at least one of these receptors. This suggests that meningococci require these receptors to cause disease.
To test this idea, the expression status of these receptors during disease will be examined by amplification from clinical samples of the repeat tracts responsible for mediating their phase variation. In addition, mutants lacking these receptors will be examined for their ability to grow in human blood.
Other objectives will focus on the suitability of these receptors as vaccine candidates. Genetic variability of the receptors in disease-causing strains and presence of antibodies to these receptors in sera from carriers will be examined. The receptors will also be tested for an ability to elicit serum bactericidal antibodies and to protect against meningococcal bacteremia.
The outcome of these studies will be evidence that a small number of antigenic variants of the haemoglobin receptors will induce broad-spectrum protection against invasive meningococcal strains.