The variable efficacy of BCG vaccination: can our metabolome solve a piece of the puzzle?

BCG, the only tuberculosis vaccine currently available, celebrated its 100^th birthday last year. Although it is one of the oldest vaccines still in use, BCG remains a bit of an enigma: the protection it provides against tuberculosis varies greatly between settings and concluding evidence as to why remains elusive. In addition, BCG not only educates the adaptive immune system, but remodels the innate immune system leading to enhanced protection against a wide variety of infectious diseases. This process is called trained immunity. However, the immune responses induced by BCG are variable, leading to inconsistent protection, and the factors causing this heterogeneity are poorly understood.

Researchers from internal medicine, including Dr. Valerie Koeken, Prof. Mihai Netea and Prof. Yang Li, set out to answer this question in collaboration with the Centre for Individualised Infection Medicine (CiiM) from Hannover. Considering the important role of metabolites and metabolism for immune function, circulating metabolites were measured in a cohort of over 300 healthy individuals who received the BCG vaccine for the first time. Using machine learning methods, the circulating metabolome was shown to predict immune responses to BCG vaccination, although only moderately. Interestingly, mainly the innate immune response was associated with the metabolome, rather than the adaptive immune response, suggesting that metabolites play an important role in the induction of trained immunity. One metabolite, taurine, which is most notorious for being added to energy drinks, was validated in vitro to play a causal role in the induction of trained immunity. The results of this study were published on 12^th of September in PLoS Biology.

These findings underline that the metabolome can explain - to some extent - the heterogeneity in BCG-induced immune responses, which mediate the prevention of tuberculosis and other infectious diseases. Metabolic modulation may present a novel strategy to improve vaccine and trained immunity responses.

Publication

Koeken VACM, Qi C, Mourits VP, de Bree LCJ, Moorlag SJCFM, Sonawane V, Lemmers H, Dijkstra H, Joosten LAB, van Laarhoven A, Xu CJ, van Crevel R, Netea MG, Li Y. Plasma metabolome predicts trained immunity responses after antituberculosis BCG vaccination. PLoS Biology. 2022 Sep 12;20(9):e3001765. doi: 10.1371/journal.pbio.3001765. PMID: 36094960; PMCID: PMC9499240.

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