Mackenzie, J.E.; (2006) Immunomodulatory properties of meningococcal outer membrane vesicles. Doctoral thesis , University of London.

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Abstract

Neisseria meningitidis (Nm) causes potentially fatal bacterial sepsis and meningitis in susceptible individuals, but induces protective immunity in asymptomatic carriers. Nm naturally sheds outer membrane vesicles (NOMVs) that contain a high proportion of lipopolysaccharide (LPS) and outer membrane proteins. NOMVs are known to induce serum bactericidal antibodies in mice and humans, but their inherent adjuvanticity of humoral responses toward protein and carbohydrate antigens has not been studied in detail. This thesis investigation has determined that NOMVs are potent intraperitoneal and intranasal adjuvants for model T-dependent antigens such as Ovalbumin and T-independent antigens such as dinitrophenol-ficoll. Surprisingly NOMVs had little or no effect on the primary antibody responses towards several clinically relevant capsular polysaccharides from Streptococcus pneumoniae regardless of the route of immunisation. NOMVs induced the proliferation of splenic B cells, and the production of cytokines from splenocytes and bone marrow-derived dendritic cells from not only wild-type but also LPS-hyporesponsive mice which indicates that both LPS and non-LPS components have immunomodulatory properties. Despite the potential of NOMVs inducing proinflammatory responses, preliminary results showed that intranasally applied NOMVs suppressed allergen induced or respiratory syncytial virus-induced airway eosinophilia in mouse models. Together our results provide important insights into the role of NOMVs in inducing protective immunity against meningococcal diseases, and their immunomodulatory properties that could be useful separately or synergistically in adjuvant development or immunotherapy.

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