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Unconventionally, a growing number of epidemiological, preclinical, and clinical studies demonstrate that live vaccines, including Bacillus Calmette Gu\u00e9rin (BCG), measles\u2010containing vaccines, and oral polio vaccine, induce protection through trained immunity, a form of metabolically and epigenetically mediated memory in innate immune cells and their progenitors. This concept is particularly relevant during early life, when adaptive immune responses are constrained and innate immunity represents the principal line of host defence. In this review, we discuss the unique characteristics of neonatal and infant immunity, summarize current evidence for trained immunity induced by childhood vaccines, and describe the bidirectional interplay between innate and adaptive immune memory. We further highlight the potential of trained immunity to broaden protection against severe infections, improve vaccine efficacy, and provide therapeutic opportunities for non\u2010infectious paediatric diseases, including cancer and allergic disorders. Harnessing trained immunity represents a conceptual shift in paediatric vaccinology and may guide the development of next generation vaccines that provide broader and more resilient protection during the period of greatest immunological vulnerability.<\/jats:p>","DOI":"10.1111\/apa.70751","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:22:11Z","timestamp":1790079731000},"page":"2402-2413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Trained Immunity in Childhood Vaccination"],"prefix":"10.1111","volume":"115","author":[{"given":"ChenRongRong","family":"Cai","sequence":"first","affiliation":[{"name":"Meakins\u2010Christie Laboratories Research Institute of the McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-0084","authenticated-orcid":false,"given":"Lubnaa","family":"Hossenbaccus","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7965-9200","authenticated-orcid":false,"given":"Eva","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Faculty of Health Sciences Queen's University  Kingston Ontario Canada"},{"name":"Faculty of Dental Medicine and Oral Health Sciences McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2005.11928028"},{"issue":"1","key":"e_1_2_12_3_1","first-page":"E231","article-title":"Louis Pasteur and Dom Pedro II Engaged in Rabies Vaccine Development","volume":"62","author":"Gomes M. 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