Towards the development of a universal influenza vaccine: investigating viral-vectored vaccine-induced heterosubtypic immune responses to influenza A

Influenza A viruses pose a continual threat to global society and are responsible for considerable morbidity and mortality on an annual basis. Existing seasonal vaccines must be regularly reformulated to match circulating strains and do not protect against pandemic viruses. A universal influenza vaccine capable of protecting against both seasonal and pandemic strains is a major goal of vaccine developers. In recent years there has been considerable interest in broadly neutralising antibodies that target the stem region of haemagglutinin (HA). Work in this thesis reports the design and production of several tools designed to measure anti-stem responses, namely, two recombinant chimeric HA proteins and a phage display library. In addition the development of three novel viral-vectored vaccines aimed at inducing anti-stem responses and the investigation of their immunogenicity is described. This thesis also examines the cellular events associated with the development of antibody responses in response to viral-vectored vaccination and reports on the immunogenicity of multivalent, multi-antigen viral-vectored vaccination against influenza in work towards the development of a universal influenza A vaccine.