The diversity of meningococcal Opa proteins and their human receptor: implications for disease susceptibility and vaccine design.
Dr Andrew Pollard, Dr Martin Maiden, Professor Dominic Kwiatkowski, Professor Michael Levin, Professor Richard Moxon, Professor Simon Kroll
- Start Date:
01 January 2002
John Radcliffe Hospital, Oxford, UK, Oxford University, Oxford, UK
Despite the recent introduction of a vaccine against serogroup C meningococci, invasive disease caused by Neisseria meningitidis remains the leading infectious cause of death in early childhood in the United Kingdom. A strategy for prevention of invasive disease, which is yet to be fully explored, is immunisation with the aim of inhibiting specific meningococcal interactions with human cells, for example, attachment in the nasopharynx. Although a number of bacterial surface structures, including type-IV pili and the Opc protein have been found to be important in meningococcal colonisation of host tissues and in invasive disease, a primary means of intimate attachment between the meningococcus and its host is the interaction between meningococcal Opacity (Opa) proteins and human carcinoembryonic-antigen cell adhesion molecules (CEACAMs). This project will investigate protein sequence diversity of the meningococcal Opa proteins, in combination with the diversity of the human receptor for this protein, CEACAM and explore the relative importance of Opa and CEACAM diversity in meningococcal pathogenesis. We will also examine generation of Opa sequence-specific antibody after meningococcal infection with particular Opa-expressing isolates and compare antibody repertoires in children and adults.
We will use these data to evaluate targeted health care interventions such as the identification of individuals with particular susceptibility to meningococcal disease, or the development of vaccines directed against Opa protein variants associated with disease by blocking adhesion and providing protection against invasion.