Abstract:
The generation of enduring protective immunity by vaccines is of utmost importance.
Intriguingly, there is considerable variation in the efficacy of vaccines amongst
individuals. Various studies have shown that normal flora of gastrointestinal tract plays
a vital role in maintaining host homeostasis and immunity. Since gut microbiome is also
extremely variable between individuals, we speculate that it might impact individual’s
response to vaccines. Consequently, we administered broad spectrum antibiotics
cocktail to induce gut dysbiosis and monitored its impact on the generation of longlasting memory T cells and thereby BCG vaccine efficacy. Interestingly, gut dysbiosis
significantly decreased the activation of CD4+ T cells and CD8+ T cells. Further, there
was decline in the frequency of memory CD4+ T cells and CD8+ T cells in lungs and
secondary lymphoid organs of the vaccinated animals. Moreover, it dampened the IFN-γ
and TNF-α secretion and proliferation of Mtb-specific T cells. Most importantly, dysbiosis
hampered Mtb clearance in vaccinated animals, as evidenced by increase in the colony
forming units (CFUs) in lungs and spleen. Our findings indicate that gut dysbiosis can be
one of the major factors responsible for variable efficacy of TB vaccines across the world.
