The highly integrated INCENTIVE consortium represents true partnership between Indian and European/US groups that addresses the global health and economic challenge posed by influenza infections, to reduce the worldwide burden resulting from outbreaks. INCENTIVE’s strategic goals are to provide seminal knowledge on the underlying mechanisms of poor responsiveness to influenza vaccines in vulnerable individuals and advance the development of two next generation universal influenza vaccines. This is achieved by pursing the following specific objectives: 1) address the current knowledge gap by performing comprehensive immunome profiling of responders and non-responders to licensed influenza vaccines in infants, children, adults and elderly in parallel phase IV trials in Europe and India to identify the underlying mechanisms of vaccine responsiveness in different vulnerable populations and ethnical groups; 2) advance the development of two next generation universal vaccines, including an antigen presenting cell-targeted nucleic acid vaccine up to proof-of-concept for vaccine efficacy in non-human primates, and a computationally-derived second generation COBRA (Computationally-Optimized Broadly-Reactive Antigens) vaccine up to clinical development, comprising a phase I trial in Europe, a phase II trial in India and efficacy studies using an influenza controlled human challenge model; 3) identify predictive biomarkers of responsiveness to vaccination to develop new diagnostics; 4) implement comprehensive technology transfer and harmonization activities for immunological analysis and data integration; and 5) perform a health systems and investment analysis, and discrete choice experiments to assess the suitability of the developed technologies for low- and middle-income countries and to identify potential downstream constraints that might affect uptake by health care systems.