Malnourishment and expanded microbiome maintain superior efficacy of the recombinant tuberculosis vaccine BCG::ESAT-6-PE25SS
Puri, M.; Kumar, M.; Nagaraja, H.; Sathkumara, H.; Rowarth, S.; Robertson, K.; Subbian, S.; Warner, J.; Rush, C.; Ruscher, R.; Field, M.; Kupz, A.
Show abstract
Tuberculosis (TB) remains the leading cause of infectious mortality. The limited efficacy of the only TB vaccine, Bacille Calmette-Guerin (BCG) against pulmonary disease necessitates improved vaccines. Host factors such as malnutrition and microbiome composition shape immune responses in humans, though these factors are overlooked in preclinical vaccine evaluation. Here we show that a recombinant BCG strain, BCG::ESAT-6-PE25SS, confers superior protection compared to BCG across murine models of malnutrition, antibiotic-induced dysbiosis and environmentally enriched microbiota. Unexpectedly, malnourished mice displayed reduced Mycobacterium tuberculosis (Mtb) burden, associated with altered host metabolism and immune composition. Microbiome disruption increased TB susceptibility, whereas diversification of microbiota enhanced resistance and immune heterogeneity. Vaccine efficacy correlated with enrichment of known immunomodulatory microbial taxa. These findings suggest diet-microbiome-immunity interactions as potential key determinants of TB pathogenesis and provide evidence for the importance of vaccine candidate evaluation under physiologically relevant co-morbid conditions
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Maternal γδ T Cells Shape Offspring Pulmonary Type-2 Immunity In A Microbiota-Dependent Manner 93%
- A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity 93%
- Maturation of Human Intestinal Epithelial Cell Layers Fortifies the Apical Surface against Salmonella Attack 92%
Similar papers in this journal
- Dynamic colonization of microbes and their functions after fecal microbiota transplantation for inflammatory bowel disease 94%
- Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics 93%
- Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity. 92%
Similar papers in this journal
- Early and Delayed STAT1-Dependent Responses Drive Local Trained Immunity of Macrophages in the Spleen 93%
- Parallel signatures of mammalian domestication and human industrialization in the gut microbiota 92%
- Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.