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Peer-reviewedCC BY-NC-ND 4.0NPJ Vaccines

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

  1. 1Department of Infectious Disease Immunology, Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark
  2. 2Novo Nordisk Foundation Initiative for Vaccines and Immunity, NIVI Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
  3. 3Countermeasure Development, Evaluation and Preparedness (CDEP), United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, UK

Abstract

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.

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BibTeX
@article{woodworth2026postexposure,
  title = {{Post-exposure vaccination with an adjuvanted protein subunit vaccine, but not BCG, protects mice and guinea pigs against M. tuberculosis}},
  author = {Joshua S. Woodworth and Claus Aagaard and Francisco J. Salguero and Laura Hunter and Thomas Lindenstrøm and Simon Clark and Rasmus Mortensen},
  journal = {NPJ Vaccines},
  year = {2026},
  month = jul,
  doi = {10.1038/s41541-026-01509-6},
  url = {https://doi.org/10.1038/s41541-026-01509-6},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Post-exposure vaccination with an adjuvanted protein subunit vaccine, but not BCG, protects mice and guinea pigs against M. tuberculosis
AU  - Joshua S. Woodworth
AU  - Claus Aagaard
AU  - Francisco J. Salguero
AU  - Laura Hunter
AU  - Thomas Lindenstrøm
AU  - Simon Clark
AU  - Rasmus Mortensen
PY  - 2026
DA  - 2026/07/08
JO  - NPJ Vaccines
DO  - 10.1038/s41541-026-01509-6
UR  - https://doi.org/10.1038/s41541-026-01509-6
AB  - 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.
SN  - 2059-0105
ER  -