Modulation of human immune responses to MenB by mucosal vaccination,

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Prevention of meningococcal disease through vaccination is a key public health priority.  Natural carriage of Nm and related bacteria are associated with the development of protective immunity.  However, attempts to mimic this process through the use of injectable Nm serogroup B (MenB) vaccines have thus far been unsuccessful.   We hypothesise that if future MenB vaccines are to be successful, the immunological response needs to incorporate cellular and humoral immune pathways that mirror those induced by natural colonisation. In a series of human experimental studies we will (1) Determine the ability of mucosal immunisation with meningococcal antigens to augment pre-existing mucosal immunity to NM; and (2) Investigate whether mucosal immunisation appropriately primes naïve individuals who have little pre-existing mucosal immunity to Nm.  To evaluate mucosal immunity at the cellular level we will use a human experimental system optimised in Bristol in which subjects are vaccinated prior to routine tonsillectomy.   We will use a novel nasal vaccine device to maximise vaccine distribution to the mucosal surface.  Our findings will provide an insight into how closely mucosal immunisation mirrors the protective immunity acquired naturally with age.  Vaccination will enable us to probe the mechanisms that underlie this process and establish the link between immunological memory in both the mucosal and systemic compartments and proposed correlates of protection (SBA, opsonophagocytosis and mucosal lgA).  The work will inform the design of novel vaccine strategies and allow the rational testing of new vaccines as they become available.