BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines

The tuberculosis (TB) vaccine Bacillus Calmette‐Guérin (BCG) was introduced 100 years ago, but as it provides insufficient protection against TB disease, especially in adults, new vaccines are being developed and evaluated. The discovery that BCG protects humans from becoming infected with Mycobacte...

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Autores principales: Foster, Mitchell, Hill, Philip C., Setiabudiawan, Todia Pediatama, Koeken, Valerie A. C. M., Alisjahbana, Bachti, van Crevel, Reinout
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252066/
https://www.ncbi.nlm.nih.gov/pubmed/33709421
http://dx.doi.org/10.1111/imr.12965
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author Foster, Mitchell
Hill, Philip C.
Setiabudiawan, Todia Pediatama
Koeken, Valerie A. C. M.
Alisjahbana, Bachti
van Crevel, Reinout
author_facet Foster, Mitchell
Hill, Philip C.
Setiabudiawan, Todia Pediatama
Koeken, Valerie A. C. M.
Alisjahbana, Bachti
van Crevel, Reinout
author_sort Foster, Mitchell
collection PubMed
description The tuberculosis (TB) vaccine Bacillus Calmette‐Guérin (BCG) was introduced 100 years ago, but as it provides insufficient protection against TB disease, especially in adults, new vaccines are being developed and evaluated. The discovery that BCG protects humans from becoming infected with Mycobacterium tuberculosis (Mtb) and not just from progressing to TB disease provides justification for considering Mtb infection as an endpoint in vaccine trials. Such trials would require fewer participants than those with disease as an endpoint. In this review, we first define Mtb infection and disease phenotypes that can be used for mechanistic studies and/or endpoints for vaccine trials. Secondly, we review the evidence for BCG‐induced protection against Mtb infection from observational and BCG re‐vaccination studies, and discuss limitations and variation of this protection. Thirdly, we review possible underlying mechanisms for BCG efficacy against Mtb infection, including alternative T cell responses, antibody‐mediated protection, and innate immune mechanisms, with a specific focus on BCG‐induced trained immunity, which involves epigenetic and metabolic reprogramming of innate immune cells. Finally, we discuss the implications for further studies of BCG efficacy against Mtb infection, including for mechanistic research, and their relevance to the design and evaluation of new TB vaccines.
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spelling pubmed-82520662021-07-07 BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines Foster, Mitchell Hill, Philip C. Setiabudiawan, Todia Pediatama Koeken, Valerie A. C. M. Alisjahbana, Bachti van Crevel, Reinout Immunol Rev Invited Reviews The tuberculosis (TB) vaccine Bacillus Calmette‐Guérin (BCG) was introduced 100 years ago, but as it provides insufficient protection against TB disease, especially in adults, new vaccines are being developed and evaluated. The discovery that BCG protects humans from becoming infected with Mycobacterium tuberculosis (Mtb) and not just from progressing to TB disease provides justification for considering Mtb infection as an endpoint in vaccine trials. Such trials would require fewer participants than those with disease as an endpoint. In this review, we first define Mtb infection and disease phenotypes that can be used for mechanistic studies and/or endpoints for vaccine trials. Secondly, we review the evidence for BCG‐induced protection against Mtb infection from observational and BCG re‐vaccination studies, and discuss limitations and variation of this protection. Thirdly, we review possible underlying mechanisms for BCG efficacy against Mtb infection, including alternative T cell responses, antibody‐mediated protection, and innate immune mechanisms, with a specific focus on BCG‐induced trained immunity, which involves epigenetic and metabolic reprogramming of innate immune cells. Finally, we discuss the implications for further studies of BCG efficacy against Mtb infection, including for mechanistic research, and their relevance to the design and evaluation of new TB vaccines. John Wiley and Sons Inc. 2021-03-12 2021-05 /pmc/articles/PMC8252066/ /pubmed/33709421 http://dx.doi.org/10.1111/imr.12965 Text en © 2021 The Authors. Immunological Reviews published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Invited Reviews
Foster, Mitchell
Hill, Philip C.
Setiabudiawan, Todia Pediatama
Koeken, Valerie A. C. M.
Alisjahbana, Bachti
van Crevel, Reinout
BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines
title BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines
title_full BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines
title_fullStr BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines
title_full_unstemmed BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines
title_short BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines
title_sort bcg‐induced protection against mycobacterium tuberculosis infection: evidence, mechanisms, and implications for next‐generation vaccines
topic Invited Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252066/
https://www.ncbi.nlm.nih.gov/pubmed/33709421
http://dx.doi.org/10.1111/imr.12965
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