Guthrie, Terry; (2002) Characterisation of immune responses toward meningococcal antigens. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Neisseria meningitidis is the causative agent of meningococcal disease, which remains a significant cause of mortality and morbidity in both developing and developed countries. Protection towards meningococcal disease is thought to be dependent upon the presence of serum bactericidal antibodies. Capsular polysaccharides derived from serogroup B organisms have shown poor immunogenicity and may share structural similarities with carbohydrates expressed on neural tissues. Consequently, other surface antigens are currently being explored as possible vaccine candidates. Natural outer membrane vesicles (NOMV) consist of membranes released by meningococci during growth and thus are representative of the outer membrane. Our investigations have focused upon analysing the humoral immune response towards NOMV in mice. NOMV were delivered by systemic immunisation and intranasal immunisation. Humoral immune responses were analysed by determining the amount and isotype/subclass profile of antibodies toward NOMV and their components. Secondary and local lymphoid tissues were also analysed for the presence of NOMV- specific antibody forming cells. Our studies demonstrate that NOMV are immunogenic and can elicit bactericidal antibodies when administered by either intranasal or systemic immunisation. However, differences were apparent in the levels and isotype/subclass profiles of antibodies observed depending on the route of immunisation and the immunisation protocol used. The magnitude and kinetics of the B cell response in secondary lymphoid tissues was also found to vary. More importantly, intranasal immunisation induced substantial and long-lived B cell responses towards NOMV in the nasal-associated lymphoid tissues. Our studies conclude that intranasal immunisation with NOMV represents a novel method of delivering meningococcal antigens which can elicit bactericidal antibodies and establish local B cell mediated immunity.

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