Trained immunity is a long-term functional modification of cells in the innate immune system which leads to an altered response to a second unrelated challenge.[1] For example, the BCG vaccine leads to a reduction in childhood mortality caused by unrelated infectious agents.[2] The term "innate immune memory" is sometimes used as a synonym for the term trained immunity[3][4] which was first coined by Mihai Netea in 2011.[5] The term "trained immunity" is relatively new – immunological memory has previously been considered only as a part of adaptive immunity – and refers only to changes in innate immune memory of vertebrates.[6][7] This type of immunity is thought to be largely mediated by epigenetic modifications. The changes to the innate immune response may last up to several months, in contrast to the classical immunological memory (which may last up to a lifetime), and is usually unspecific because there is no production of specific antibodies/receptors.[8] Trained immunity has been suggested to possess a transgenerational effect, for example the children of mothers who had also received vaccination against BCG had a lower mortality rate than children of unvaccinated mothers.[9] The BRACE trial is currently assessing if BCG vaccination can reduce the impact of COVID-19 in healthcare workers.[10] Other vaccines are also thought to induce immune training such as the DTPw vaccine. [11]
^Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, et al. (June 2020). "Defining trained immunity and its role in health and disease". Nature Reviews. Immunology. 20 (6): 375–388. doi:10.1038/s41577-020-0285-6. PMC 7186935. PMID 32132681.
^Aaby, Peter; Roth, Adam; Ravn, Henrik; Napirna, Bitiguida Mutna; Rodrigues, Amabelia; Lisse, Ida Maria; Stensballe, Lone; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Lund, Najaaraq; Biering-Sørensen, Sofie (2011-07-15). "Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?". The Journal of Infectious Diseases. 204 (2): 245–252. doi:10.1093/infdis/jir240. ISSN 1537-6613. PMID 21673035.
^Levy O, Wynn JL (2013). "A prime time for trained immunity: innate immune memory in newborns and infants". Neonatology. 105 (2). US National Library of Medicine Introduction Line 6 Netea and colleagues recently coined the term trained immunity: 136–141. doi:10.1159/000356035. PMC 3946366. PMID 24356292.
^"Trained Therapeutix Discovery founders Mihai Netea and Leo Joosten have revealed that the innate immune systems also has adaptive characteristics. This de facto innate immune memory is called 'trained immunity'". ttxdiscovery.com. Retrieved 25 November 2022.
^Netea MG, Quintin J, van der Meer JW (May 2011). "Trained immunity: a memory for innate host defense". Cell Host & Microbe. 9 (5): 355–61. doi:10.1016/j.chom.2011.04.006. PMID 21575907.
^Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, et al. (April 2016). "Trained immunity: A program of innate immune memory in health and disease". Science. 352 (6284): aaf1098. doi:10.1126/science.aaf1098. PMC 5087274. PMID 27102489.
^Gourbal B, Pinaud S, Beckers GJ, Van Der Meer JW, Conrath U, Netea MG (May 2018). "Innate immune memory: An evolutionary perspective" (PDF). Immunological Reviews. 283 (1): 21–40. doi:10.1111/imr.12647. PMID 29664574. S2CID 4891922.
^Pradeu T, Du Pasquier L (May 2018). "Immunological memory: What's in a name?" (PDF). Immunological Reviews. 283 (1): 7–20. doi:10.1111/imr.12652. PMID 29664563. S2CID 4893762.
^Berendsen ML, Øland CB, Bles P, Jensen AK, Kofoed PE, Whittle H, et al. (April 2020). "Maternal Priming: Bacillus Calmette-Guérin (BCG) Vaccine Scarring in Mothers Enhances the Survival of Their Child With a BCG Vaccine Scar". Journal of the Pediatric Infectious Diseases Society. 9 (2): 166–172. doi:10.1093/jpids/piy142. PMID 30715451.
^Pittet, Laure F.; Messina, Nicole L.; Gardiner, Kaya; Orsini, Francesca; Abruzzo, Veronica; Bannister, Samantha; Bonten, Marc; Campbell, John L.; Croda, Julio; Dalcolmo, Margareth; Elia, Sonja (2021-10-28). "BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)". BMJ Open. 11 (10): e052101. doi:10.1136/bmjopen-2021-052101. ISSN 2044-6055. PMC 8557250. PMID 34711598.
^Stevens, Natalie E.; van Wolfswinkel, Marjolein; Bao, Winnie; Ryan, Feargal J.; Brook, Byron; Amenyogbe, Nelly; Marshall, Helen S.; Lynn, Miriam A.; Kollmann, Tobias R.; Tumes, Damon J.; Lynn, David J. (2022-03-08). "Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice". Vaccine. 40 (11): 1594–1605. doi:10.1016/j.vaccine.2021.03.084. ISSN 1873-2518. PMID 33895015. S2CID 233399069.
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