Infection, Immunology and Translational Medicine-'Towards the development of auniversal influenza vaccine:Investigation of heterosubtypic humoral and cellular immune responses to influenza induced by vaccincation with viral (360G-Wellcome-097113_Z_11_Z)

Seasonal influenza epidemics and pandemics are associated with a non-trivial mortality, morbidity and carry a heavy socioeconomic burden. Vaccination is still the primary strategy for the prevention and control of influenza despite the limitations of currently licensed vaccines and their requirement of periodic reformulation and annual revaccination of at-risk individuals. A first generation T-cell inducing influenza vaccine developed at the Jenner Institute has demonstrated partial efficacy in a human trial. However, there is further workto be done in terms of targeting other conserved antigenic sites that can efficaciously provide heterosubtypic B cell immunity between multiple strains of influenza. We hypothesise that by targeting both arms of the adaptive immune system through rational vaccine design this could provide the highest level of protection against seasonal and pandemic flu. I will assess this by (i) designing new viral vector vaccines that targetcellular and humoral immunity, (ii) testing appropriate regimens in preclinical studies, (iii) measuring induced immunity to influenza antigens and (iv) delineating the mechanisms of B cell memory induction. As we are interested in assessing the use of these candidate vaccines in combination with or as a booster to seasonal influenza vaccination I will investigate a best in class' regimen including our novel vaccine.