Defining the immune response to nasopharyngeal colonisation by the commensal Neissaria lactamica

Upper respiratory tract colonisation by the commensal Neisseria lactamica (Nlac) protects against meningococcal disease. The ability to harness this natural effect could simplify our strategy for disease prevention, however the associated mechanism is currently unknown. There is no evidence to suggest that this effect is due to bacterial competition, and the production of cross-reactive meningococcal serum bactericidal antibody does not occur. I therefore postulate that an alternative adaptive cross-reactive immune mechanism may be responsible for protection against meningococcal disease. My strategy is to firstly compare the effects that Nlac and N. meningitidis (Nmen) have on naïve T-cell priming. I will subsequently utilise a human challenge model to characterise the T-cell/B-cell memory responses induced by Nlac colonisation. If a T-cell memory response is detectable in Nlac colonised participants, I will characterise it. If not, I will identify the mechanism of immune tolerance in vitro. Finally, I will determine whether specific mucosal immunological signatures are associated with Nlac/Nmen/non-Neisseria spp. carriage. The results will improve our understanding of host-commensal interactions and inform future vaccine design, particularly in cases where commensal species are utilised as immunogen vectors, or where the elimination of mucosal carriage is paramount.