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<p>Tuberculosis (TB) remains a global health priority and vaccines targeting populations with prior <i>Mycobacterium tuberculosis</i> (Mtb) exposure are predicted to most rapidly impact epidemic control. Paradoxically, while efficacy trials are primarily targeting previously Mtb-exposed populations, preclinical testing largely relies on Mtb-naïve animal models. We introduce two post-exposure models, a murine reinfection model and a previously unreported guinea pig reactivation model, and evaluate the efficacy of the adjuvanted protein subunit vaccine H107/CAF®01 compared to Bacillus Calmette-Guérin (BCG). Consistent with clinical and human population data, we demonstrate that BCG fails to confer significant protection in these post-Mtb-exposed settings. In contrast, H107/CAF®01 imprints distinct Th17 responses and provides robust and consistent protection, reducing both the bacterial burden and infection-associated tissue pathology. These findings support the development of H107 as a vaccine candidate in previously Mtb-exposed and infected populations and underscores the importance of evaluating TB vaccines in animal models that reflect prior exposure.</p>

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Post-exposure vaccination with an adjuvanted protein subunit vaccine, but not BCG, protects mice and guinea pigs against M. tuberculosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Joshua S. Woodworth,
  • Claus Aagaard,
  • Francisco J. Salguero,
  • Laura Hunter,
  • Thomas Lindenstrøm,
  • Simon Clark,
  • Rasmus Mortensen

摘要

Tuberculosis (TB) remains a global health priority and vaccines targeting populations with prior Mycobacterium tuberculosis (Mtb) exposure are predicted to most rapidly impact epidemic control. Paradoxically, while efficacy trials are primarily targeting previously Mtb-exposed populations, preclinical testing largely relies on Mtb-naïve animal models. We introduce two post-exposure models, a murine reinfection model and a previously unreported guinea pig reactivation model, and evaluate the efficacy of the adjuvanted protein subunit vaccine H107/CAF®01 compared to Bacillus Calmette-Guérin (BCG). Consistent with clinical and human population data, we demonstrate that BCG fails to confer significant protection in these post-Mtb-exposed settings. In contrast, H107/CAF®01 imprints distinct Th17 responses and provides robust and consistent protection, reducing both the bacterial burden and infection-associated tissue pathology. These findings support the development of H107 as a vaccine candidate in previously Mtb-exposed and infected populations and underscores the importance of evaluating TB vaccines in animal models that reflect prior exposure.