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A recent publication by a Stanford scientist, Bali Pukendran, reviews how the microbiome may play a key role in vaccines efficacy.
Multiples examples have highlighted the role of the microbiota. Earlier studies have evaluated the role of the microbiota small animal models in which depletion of their microbiota by antibiotics or the testing with germ-free animals resulted in reduced vaccine efficacies. Other studies in human have helped understand how the microbiome influences vaccine's responses by monitoring the vaccine's signature. The use of artificial intelligence has been used to predict immune responses.
Immunization with influenza vaccines led to the discovery of potential links with the microbiota. The inactivated influenza vaccine induces expression of Toll-like-receptor 5 (TLR5), a key protein recognizing bacterial components and triggering an innate immune response. Mice deficient in tlr5 induce poor anti-influenza antibody responses upon vaccination. Similar results have been observed with an adjuvant-free polio vaccine, but not with vaccines containing adjuvants, suggesting that the microbiota may act as an endogenous adjuvant, and may play an even more important role when the individuals have no pre-existing immunity against the pathogen the are immunized against.
Several studies have revealed that in addition to specific gene signatures, antibiotics also lead to significant changes in the blood metabolome, including changes in bile acids that have been shown to modulate inflammatory responses in humans. Furthermore, age may increase gut permeability, exacerbating the effects of the bacterial metabolome and perhaps playing a role in the limited vaccine efficacy observed in elderly patients.
These findings highlights the importance of avoiding antibiotic use during vaccination, especially in children, where pre-existing responses may be limited. They also highlight the importance to stratify patients in vaccine trials by their microbiomes and bacterial metabolomes, to better elucidate which patients better response to future experimental vaccines.
Published in Science (29 November , 2019):
https://doi.org/10.1126/science.aau6975
