Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review

IntroductionBCG vaccination can have heterologous or non-specific effects (NSE) that confer resistance against pathogens other than its target Mycobacterium tuberculosis, but the underlying mechanisms are not fully understood.MethodsWe conducted a systematic review synthesising existing literature o...

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Main Authors: Louis Torracinta, Nino Gogichadze, Rachel Tanner
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1567111/full
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author Louis Torracinta
Nino Gogichadze
Rachel Tanner
author_facet Louis Torracinta
Nino Gogichadze
Rachel Tanner
author_sort Louis Torracinta
collection DOAJ
description IntroductionBCG vaccination can have heterologous or non-specific effects (NSE) that confer resistance against pathogens other than its target Mycobacterium tuberculosis, but the underlying mechanisms are not fully understood.MethodsWe conducted a systematic review synthesising existing literature on immune mechanisms mediating the heterologous/NSE of BCG. Searches were conducted using MEDLINE and Scopus.Results1032 original records were identified, of which 67 were deemed eligible. Several potentially relevant immune pathways were identified, although there may be variation by pathogen. Recent studies have focused on trained immunity whereby innate cells, or the hematopoietic stem and progenitor cells from which they are derived, undergo epigenetic and metabolic reprogramming allowing them to respond more effectively to antigen exposures unrelated to the original stimulus. However, other processes such as granulopoiesis and cross-reactive adaptive immunity may also play a role. Heterologous immunity and NSEs may be influenced by several endogenous and exogenous variables.DiscussionWe discuss the quality of available data, the importance of understanding mechanisms of heterologous protection, and its implications for vaccination strategies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023400375, identifier CRD42023400375.
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spelling doaj-art-e34945a2f6fe43e7bce749ab4d6ec0612025-08-20T03:53:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15671111567111Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic reviewLouis Torracinta0Nino Gogichadze1Rachel Tanner2Medical Sciences Division, University of Oxford, Oxford, United KingdomExperimental Tuberculosis Unit, Microbiology Department, Germans Trias i Pujol Research Institute (IGTP) and Hospital (HUGTIP), Badalona, SpainDepartment of Biology, University of Oxford, Oxford, United KingdomIntroductionBCG vaccination can have heterologous or non-specific effects (NSE) that confer resistance against pathogens other than its target Mycobacterium tuberculosis, but the underlying mechanisms are not fully understood.MethodsWe conducted a systematic review synthesising existing literature on immune mechanisms mediating the heterologous/NSE of BCG. Searches were conducted using MEDLINE and Scopus.Results1032 original records were identified, of which 67 were deemed eligible. Several potentially relevant immune pathways were identified, although there may be variation by pathogen. Recent studies have focused on trained immunity whereby innate cells, or the hematopoietic stem and progenitor cells from which they are derived, undergo epigenetic and metabolic reprogramming allowing them to respond more effectively to antigen exposures unrelated to the original stimulus. However, other processes such as granulopoiesis and cross-reactive adaptive immunity may also play a role. Heterologous immunity and NSEs may be influenced by several endogenous and exogenous variables.DiscussionWe discuss the quality of available data, the importance of understanding mechanisms of heterologous protection, and its implications for vaccination strategies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023400375, identifier CRD42023400375.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1567111/fullBCGheterologous effects of vaccinationtrained immunityT cellshumoral immunitytuberculosis
spellingShingle Louis Torracinta
Nino Gogichadze
Rachel Tanner
Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
Frontiers in Immunology
BCG
heterologous effects of vaccination
trained immunity
T cells
humoral immunity
tuberculosis
title Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
title_full Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
title_fullStr Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
title_full_unstemmed Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
title_short Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
title_sort immune mechanisms mediating the heterologous effects of bcg vaccination a systematic review
topic BCG
heterologous effects of vaccination
trained immunity
T cells
humoral immunity
tuberculosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1567111/full
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