title: BCG-associated heterologous immunity, a historical perspective: intervention studies in animal models of infectious diseases.
abstract: The WHO Special Advisory Group of Experts (SAGE) review of the available epidemiological and trial evidence in humans concluded that bacillus Calmette-Guérin (BCG) vaccination leads to beneficial heterologous ('non-specific') effects, specifically on all-cause mortality. Randomized controlled trials showing this beneficial effect suggest improved survival is the result of enhanced protection against infection. This paper reviews the available evidence for the attenuating effects of BCG vaccine on experimental infections in animal models, including protection from bacteria, viruses, parasites and fungi. The reviewed studies suggest that BCG activates multiple immune pathways and that the basis for BCG-associated heterologous immunity may vary by pathogen. Modern immunological and molecular methods, exemplified by 'vaccinomics', are well placed to further investigate the basis of BCG's heterologous effects using a systems biology approach.
authors.affiliation: Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital Melbourne, Parkville, Vic 3052, Australia Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Vic 3052, Australia Infectious Diseases & Microbiology Research Group, Murdoch Children's Research Institute, Parkville, Vic 3052, Australia bridget.freyne@rch.org.au.
authors.forename: Bridget
authors.initials: B
authors.lastname: Freyne
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, 6041 Charleroi, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
authors.affiliation: Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital Melbourne, Parkville, Vic 3052, Australia Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Vic 3052, Australia Infectious Diseases & Microbiology Research Group, Murdoch Children's Research Institute, Parkville, Vic 3052, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
mesh_terms: D026683:Advisory Committees; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D064789:Immunity, Heterologous / Q000187:drug effects* / Q000276:immunology; D009163:Mycobacterium bovis / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic; D014376:Tuberculosis / Q000266:history / Q000276:immunology / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine
keywords: Animal; BCG; Heterologous; Non-specific; Vaccine