Innate immune memory induced by vaccines

An ever-growing list of stimuli, inc. vaccines, induce innate immune memory. It is mediated by the metabolic and epigenetic reprogramming of HSPC, which is preserved during their differentiation into myeloid cells. It results in modified innate responses against a secondary challenge. We studied the dynamic of and interactions between innate and adaptive response to Modified Vaccinia virus Ankara (MVA), a live attenuated vaccine, which is stockpiled against smallpox, currently used against monkeypox and a promising recombinant vaccine vector. Depending on its route of delivery to macaques, MVA prime elicited late phenotypic changes in blood neutrophils, monocytes and DCs. This long-term innate immunological imprinting modulated the innate and the secondary Ab responses to MVA boost. In a new study, we analyzed blood and bone marrow cells up to a year post-MVA immunization to link the early demand-adapted myelopoiesis and innate responses to trained immunity. We used a combination of functional assays, mass cytometry, and ATAC-Seq. Our results provide a better understanding of innate immune memory kinetic, features and mechanisms, which could be harnessed to improve vaccines and to promote novel immunomodulatory strategies.