title: Unravelling the nature of non-specific effects of vaccines-A challenge for innate immunologists.
abstract: Epidemiological observations have shown that vaccines can influence morbidity and mortality more than can be ascribed to target-disease immunity. A growing number of immunological studies have helped identify possible biological mechanisms to explain these so-called nonspecific effects (NSE) of vaccines, including heterologous T-cell reactivity and innate immune memory or 'trained innate immunity', which involves epigenetic reprogramming of innate immune cells. Here, we review the epidemiological evidence for NSE as well as human, animal and in vitro immunological data that could explain these NSE, and discuss priorities for future epidemiologic and immunologic studies to further unravel the biology and optimize the benefits of current and new vaccines.
authors.affiliation: Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark; Department of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Kristoffer Jarlov
authors.initials: KJ
authors.lastname: Jensen
authors.affiliation: Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark; Bandim Health Project, Indepth network, Bissau, Guinea-Bissau; OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
authors.affiliation: Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: reinout.vancrevel@radboudumc.com.
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D006801:Humans; D064789:Immunity, Heterologous; D007113:Immunity, Innate; D007156:Immunologic Memory; D008214:Lymphocytes / Q000502:physiology*; D009163:Mycobacterium bovis / Q000276:immunology*; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines
keywords: Epigenetic; Non-specific effects; Trained immunity; Vaccination