Despite the rapid development of various SARS-CoV-2 vaccines, the control of the pandemic is hampered by the constant emergence of SARS-CoV-2 variants escaping vaccine-induced immunity and the waning of immunity. SOLVE will tackle these challenges by deciphering the mechanisms of induction of long-lasting immunity and evaluating new vaccine platforms. To achieve this goal, an integrated plan has been developed including six pillars: 1) Vaccine discovery and design; 2) Head-to-head evaluation of the immune response and long-lasting immunity induced by four vaccine platforms in the preclinical setting; 3) Validation of the pre-clinical results in an experimental medicine trial (EMT); 4) Immune mechanisms of long-lasting immunity; 5) Data Science; 6) Determinants of population adherence to vaccination. New immunogens including key mutations from most recent variants in RBD and Nucleocapsid sequences highly conserved across Sarbecoviruses, will be delivered through: antigen-targeting to dendritic cells (DC), i.e., CD40 DC-targeting, nanoparticles, a MVA vector and 2nd generations of mRNAs. SOLVE will evaluate in depth the immunogenicity of these vaccines in the preclinical setting, and in an EMT testing two vaccines, i.e., CD40 DC-targeting and MVA with available GMP clinical lots. SOLVE will benefit from the most advanced technologies to identify the mechanisms of long-lasting immunity. Integrative analyses of high throughput data, including from large cohorts, will provide insights for identification of factors (demographics, vaccines, immunity) which impact quality and longevity of immunity. SOLVE will investigate stakeholders’s perspective on the acceptability of large vaccination campaigns to improve implementation of next generation of vaccines in a preparedness track. The consortium gathers 8 renowned public/private institutions supported by a governance facilitating fast sharing of information to keep up with a tight schedule imposed by the pandemic.