title: Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines.
abstract: An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can provide protection against certain infections in vaccination models independently of lymphocytes. This process is regulated through epigenetic reprogramming of innate immune cells and has been termed "trained immunity." It has been hypothesized that induction of trained immunity is responsible for the protective, nonspecific effects induced by vaccines, such as BCG, measles vaccination, and other whole-microorganism vaccines. In this review, we will present the mechanisms of trained immunity responsible for the long-lasting effects of vaccines on the innate immune system.
authors.affiliation: *Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; and Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Copenhagen, Denmark.
authors.forename: Bastiaan A
authors.initials: BA
authors.lastname: Blok
authors.affiliation: *Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; and Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Copenhagen, Denmark.
authors.forename: Rob J W
authors.initials: RJ
authors.lastname: Arts
authors.affiliation: *Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; and Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Copenhagen, Denmark.
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
authors.affiliation: *Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; and Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Copenhagen, Denmark.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
authors.affiliation: *Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; and Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Copenhagen, Denmark mihai.netea@radboudumc.nl.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines
keywords: NK cells; heterologous immunity; innate immune memory; monocytes/macrophages; vaccination