Broadly protective influenza vaccines paving the road towards the clinic

Influenza remains a major global health issue, causing serious morbidity, mortality, and substantial productivity loss each year. Influenza vaccines are the most effective medical countermeasure, and substantially alleviate the world burden of influenza. However, no influenza vaccine is currently licensed for use in children under 6 months of age, a group which have been shown to be at increased risk of complication from influenza infection. In addition, although the incidence and severity of annual influenza epidemics are reduced by vaccines covering the circulating strains, a mismatch between circulating virus strains and the strains included in the vaccine occasionally reduces the efficacy of the vaccine and current vaccines have limited effectiveness against influenza strains newly introduced in the human population. The identification of antibodies that bind to highly conserved epitopes of influenza surface proteins sparked efforts to develop influenza vaccines able to elicit these types of antibodies and induce protection against a broader range of influenza viruses. The work presented in this thesis explored whether the benefits of current seasonal influenza vaccines can be further expanded to protect vulnerable groups in the population, and whether seasonal vaccines could eventually be replaced by novel broadly protective influenza vaccines covering multiple influenza strains and seasons.