Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro

Diray‐Arce, Joann; Angelidou, Asimenia; Jensen, Kristoffer Jarlov; Conti, Maria Giulia; Kelly, Rachel S.; Pettengill, Matthew A.; Liu, Mark; Haren, Simon D. van; McCulloch, Scott; Michelloti, Greg; Idoko, Olubukola T.; Kollmann, Tobias R.; Kampmann, Beate; Steen, Hanno; Ozonoff, Al; Lasky‐Su, Jessica; Benn, Christine Stabell; Levy, Ofer

doi:10.1016/j.celrep.2022.110772

Cited by 19 publications

(13 citation statements)

References 89 publications

(126 reference statements)

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“…Additionally, viral replication blocks the conversion of putrescine to spermidine, preventing autophagy and slowing the hosts’ immune response ( 45 ). In this study, the increase of spermidine and spermidine conversion from putrescine suggests a conceivably positive effect of BCG in non-diabetic individuals as polyamine metabolism is altered by BCG vaccination ( 36 ), possibly due to innate immunity training mechanism.…”

Section: Discussionmentioning

confidence: 67%

“…AA is highly potent antiviral agent that renders enveloped viruses, such as SARS-CoV-2 inactive by suppressing viral replication ( 35 ). Previous studies have also shown that AA pathway up-regulated due to BCG vaccination ( 36 ). Other COVID-19 specific ceramides-related metabolite Cer(d18:1/26:1) ( 37 ) was found to be increased in BCG positive in this study.…”

Section: Discussionmentioning

confidence: 83%

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The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection

et al. 2023

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BackgroundThe cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection.MethodsSixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models.ResultsData suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively.ConclusionThis pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 83%

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection

et al. 2023

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“…Oxidized low-density lipoprotein, aldosterone, and low-density lipoprotein cholesterol have been proven to induce trained immunity (53)(54)(55). BCG immunization of infants perturbed the lipidome present in plasma, and the changes in LPCs were correlated with cytokine responses recalled in vitro 4 weeks after vaccination (56). Here, we showed that BCG-induced trained immunity could be improved by activating linoleic acid synthesis or directly supplementing with linoleic acid, suggesting that this signaling is a potential target of trained immunity-based immunotherapy and that linoleic acid or linoleic acid metabolism agonists have the potential to be used as vaccine adjuvants.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Xu,

Chen,

Huang

et al. 2024

Sci. Adv.

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Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity–inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity–inducing signaling pathway that could be used in the adjuvant development.

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“…These methods are not limited to studying the adult immune system but can also be applied to study immunity in infants. For example, whole blood stimulation with cord blood and peripheral blood of newborns was used to study the response to the Bacille Calmette–Guérin vaccine in infants [45].…”

Section: Clinical Applications Of Whole Blood Stimulationmentioning

confidence: 99%

Whole blood stimulation as a tool for studying the human immune system

Müller,

Kröger,

Schultze

et al. 2023

Eur J Immunol

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The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological and pathophysiological processes. Stimulating whole blood ex vivo is a powerful tool to investigate immune responses. In the context of clinical research, the applications of whole blood stimulation include host immunity, disease characterization, diagnosis, treatment, and drug development. Here, we summarize different setups and readouts of whole blood assays and discuss applications for preclinical research and clinical practice. Finally, we propose combining whole blood stimulation with high‐throughput technologies, such as single‐cell RNA‐sequencing, to comprehensively analyze the human immune system for the identification of biomarkers, therapeutic interventions as well as companion diagnostics.

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Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro

Cited by 19 publications

References 89 publications

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Whole blood stimulation as a tool for studying the human immune system

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