{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:37:20Z","timestamp":1791405440674,"version":"4.3.3"},"reference-count":114,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In addition to inducing pathogen-specific adaptive immune responses, vaccines can train the innate immune system, thereby providing broader host protection. This concept of trained immunity (TRIM) is well-established in benchtop laboratory science. This review aims to evaluate the current evidence of vaccine-induced TRIM and translate these findings into a clinical context. Various laboratory methods are used to assess TRIM; however, inconsistent results have been reported across non-BCG vaccine studies. Existing analyses lack exploration of the mechanistic basis of vaccine-induced TRIM, particularly epigenetic reprogramming and metabolic rewiring. Patterns emerge between vaccines: live-attenuated vaccines generally induce TRIM, as evidenced by increased inflammatory cytokine production upon restimulation, whereas non-live vaccines tend to demonstrate reduced trained immunity. Such findings are not consistently observed for mRNA vaccines, which show heterogeneous patterns. The limited variety of studies on non-BCG vaccines impacts the reliability of findings. A more comprehensive understanding of the mechanisms and outputs of TRIM induced by specific vaccines could better inform rational vaccine design. Furthermore, various modifiers can alter vaccine-induced TRIM responses, including sequence and route of administration, sex, and age. Consideration of these modifiers has important clinical implications in optimising vaccine administration for enhanced immune protection.<\/jats:p>","DOI":"10.3390\/ijms27094133","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:23:37Z","timestamp":1777987417000},"page":"4133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trained Immunity Induced by Vaccines: A Shifting Paradigm for Infant and Adult Immunity"],"prefix":"10.3390","volume":"27","author":[{"given":"Shana","family":"Singh-Anderson","sequence":"first","affiliation":[{"name":"Liggins Institute, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gio","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Liggins Institute, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3039-1597","authenticated-orcid":false,"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-9761","authenticated-orcid":false,"given":"Kuang-Chih","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-1243","authenticated-orcid":false,"given":"Gergely","family":"Toldi","sequence":"additional","affiliation":[{"name":"Liggins Institute, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained Immunity: A Memory for Innate Host Defense","volume":"9","author":"Quintin","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_2","first-page":"1000","article-title":"Respiratory Epithelial Cells Can Remember Infection: A Proof of Concept Study","volume":"221","author":"Bigot","year":"2019","journal-title":"J. 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