Post-exposure vaccination with an adjuvanted protein subunit vaccine, but not BCG, protects mice and guinea pigs against M. tuberculosis
- 1Department of Infectious Disease Immunology, Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark
- 2Novo Nordisk Foundation Initiative for Vaccines and Immunity, NIVI Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
- 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 -