A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models

Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, causing over a million deaths annually. The only licensed TB vaccine for human use, Bacille Calmette-Guérin (BCG), a mycobacteria-based live-attenuated vaccine, confers immunity to children but fails to efficiently protect...

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Main Authors: Lidia del Pozo-Ramos, Andreas Kupz
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.2025.1609136/full
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author Lidia del Pozo-Ramos
Andreas Kupz
author_facet Lidia del Pozo-Ramos
Andreas Kupz
author_sort Lidia del Pozo-Ramos
collection DOAJ
description Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, causing over a million deaths annually. The only licensed TB vaccine for human use, Bacille Calmette-Guérin (BCG), a mycobacteria-based live-attenuated vaccine, confers immunity to children but fails to efficiently protect adults from pulmonary TB. Several TB vaccine candidates have been developed over the last two decades, but some have failed to provide substantially better protection than BCG in clinical trials. Most of these vaccine candidates were initially evaluated for their protective capacity in mouse models of TB. With the availability of several mouse strains, vaccination routes and Mycobacterium tuberculosis (Mtb) challenge strains, to-date there is no consensus in the field about the predictive value of different murine models of TB, and it remains a matter of debate whether host genetics or vaccine-driven parameters primarily determine vaccine efficacy. Here we reviewed the performance of all TB vaccine candidates that have entered clinical trials over the last 25 years. We extracted protective efficacy data from all published studies that utilized mouse models to assess vaccination efficacy. The efficacy of each vaccine candidate to reduce lung bacterial burden depending on the mouse genotype, the vaccine administration route, and the Mtb challenge strain at different time-points was evaluated. Our data reveals insights into the effect of experimental parameters on vaccine performance and emphasizes the potential benefits of standardizing TB mouse models across vaccination-challenge studies to identify pre-clinical vaccine candidates with the highest potential to succeed.
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spelling doaj-art-94ac58f97adb4cbbb4d43e32952e07432025-08-20T03:12:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.16091361609136A review of the efficacy of clinical tuberculosis vaccine candidates in mouse modelsLidia del Pozo-RamosAndreas KupzTuberculosis (TB) remains one of the deadliest infectious diseases worldwide, causing over a million deaths annually. The only licensed TB vaccine for human use, Bacille Calmette-Guérin (BCG), a mycobacteria-based live-attenuated vaccine, confers immunity to children but fails to efficiently protect adults from pulmonary TB. Several TB vaccine candidates have been developed over the last two decades, but some have failed to provide substantially better protection than BCG in clinical trials. Most of these vaccine candidates were initially evaluated for their protective capacity in mouse models of TB. With the availability of several mouse strains, vaccination routes and Mycobacterium tuberculosis (Mtb) challenge strains, to-date there is no consensus in the field about the predictive value of different murine models of TB, and it remains a matter of debate whether host genetics or vaccine-driven parameters primarily determine vaccine efficacy. Here we reviewed the performance of all TB vaccine candidates that have entered clinical trials over the last 25 years. We extracted protective efficacy data from all published studies that utilized mouse models to assess vaccination efficacy. The efficacy of each vaccine candidate to reduce lung bacterial burden depending on the mouse genotype, the vaccine administration route, and the Mtb challenge strain at different time-points was evaluated. Our data reveals insights into the effect of experimental parameters on vaccine performance and emphasizes the potential benefits of standardizing TB mouse models across vaccination-challenge studies to identify pre-clinical vaccine candidates with the highest potential to succeed.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609136/fullBCGtuberculosisvaccineclinicalmouse modelshost genetics
spellingShingle Lidia del Pozo-Ramos
Andreas Kupz
A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
Frontiers in Immunology
BCG
tuberculosis
vaccine
clinical
mouse models
host genetics
title A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
title_full A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
title_fullStr A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
title_full_unstemmed A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
title_short A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
title_sort review of the efficacy of clinical tuberculosis vaccine candidates in mouse models
topic BCG
tuberculosis
vaccine
clinical
mouse models
host genetics
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609136/full
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