The project aims at unravelling the molecular and cellular mechanisms that contribute to long-term protection induced by vaccines. Early changes (hours and days) occurring at site of injection and distant sites following vaccine injection will be correlated to long lasting (beyond 12 months) induction of neutralizing antibodies and specific T and B cell memory. A particular focus will be made to the relation of immune response with vaccine antigen persistence in the organisms. Multiple omics approaches will be applied to different tissue compartments of animals vaccinated with the yellow fever vaccine (Stamaril) known to induce a remarkable durable response, to then inform the design of new generation of anti-poxvirus vaccines.