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Article ; Online: Shifting the Immune Memory Paradigm: Trained Immunity in Viral Infections.

Taks, Esther J M / Moorlag, Simone J C F M / Netea, Mihai G / van der Meer, Jos W M

2022 Volume 9, Issue 1, Page(s) 469–489

Abstract: Trained immunity is defined as the de facto memory characteristics induced in innate immune cells after exposure to microbial stimuli after infections or certain types of vaccines. Through epigenetic and metabolic reprogramming of innate immune cells ... ...

Abstract	Trained immunity is defined as the de facto memory characteristics induced in innate immune cells after exposure to microbial stimuli after infections or certain types of vaccines. Through epigenetic and metabolic reprogramming of innate immune cells after exposure to these stimuli, trained immunity induces an enhanced nonspecific protection by improving the inflammatory response upon restimulation with the same or different pathogens. Recent studies have increasingly shown that trained immunity can, on the one hand, be induced by exposure to viruses; on the other hand, when induced, it can also provide protection against heterologous viral infections. In this review we explore current knowledge on trained immunity and its relevance for viral infections, as well as its possible future uses.
MeSH term(s)	Humans ; Immunity, Innate ; Immunologic Memory ; Vaccines ; Virus Diseases
Chemical Substances	Vaccines
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2764224-0
ISSN	2327-0578 ; 2327-056X
ISSN (online)	2327-0578
ISSN	2327-056X
DOI	10.1146/annurev-virology-091919-072546
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Article ; Online: BCG vaccination-induced acquired control of mycobacterial growth differs from growth control preexisting to BCG vaccination.

van Meijgaarden, Krista E / Li, Wenchao / Moorlag, Simone J C F M / Koeken, Valerie A C M / Koenen, Hans J P M / Joosten, Leo A B / Vyakarnam, Annapurna / Ahmed, Asma / Rakshit, Srabanti / Adiga, Vasista / Ottenhoff, Tom H M / Li, Yang / Netea, Mihai G / Joosten, Simone A

Nature communications

2024 Volume 15, Issue 1, Page(s) 114

Abstract: Bacillus Calmette-Guèrin - vaccination induces not only protection in infants and young children against severe forms of tuberculosis, but also against non-tuberculosis related all-cause mortality. To delineate different factors influencing mycobacterial ...

Abstract	Bacillus Calmette-Guèrin - vaccination induces not only protection in infants and young children against severe forms of tuberculosis, but also against non-tuberculosis related all-cause mortality. To delineate different factors influencing mycobacterial growth control, here we first investigate the effects of BCG-vaccination in healthy Dutch adults. About a quarter of individuals already control BCG-growth prior to vaccination, whereas a quarter of the vaccinees acquires the capacity to control BCG upon vaccination. This leaves half of the population incapable to control BCG-growth. Single cell RNA sequencing identifies multiple processes associated with mycobacterial growth control. These data suggest (i) that already controllers employ different mechanisms to control BCG-growth than acquired controllers, and (ii) that half of the individuals fail to develop measurable growth control irrespective of BCG-vaccination. These results shed important new light on the variable immune responses to mycobacteria in humans and may impact on improved vaccination against tuberculosis and other diseases.
MeSH term(s)	Adult ; Infant ; Child ; Humans ; Child, Preschool ; BCG Vaccine ; Mycobacterium ; Tuberculosis/microbiology ; Vaccination/methods
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44252-5
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Article ; Online: Epigenetic, transcriptional, and functional characterization of myeloid cells in familial Mediterranean fever.

Röring, Rutger J / Li, Wenchao / Liu, Ruiqi / Bruno, Mariolina / Zhang, Bowen / Debisarun, Priya A / Gaal, Orsolya / Badii, Medeea / Klück, Viola / Moorlag, Simone J C F M / van de Veerdonk, Frank / Li, Yang / Joosten, Leo A B / Netea, Mihai G

iScience

2024 Volume 27, Issue 4, Page(s) 109356

Abstract: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by variation ... ...

Abstract	Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by variation in
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109356
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Article ; Online: Corrigendum: The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.

Föhse, Konstantin / Taks, Esther J M / Moorlag, Simone J C F M / Bonten, Marc J M / van Crevel, Reinout / Ten Oever, Jaap / van Werkhoven, Cornelis H / Netea, Mihai G / van de Maat, Josephine S / Hoogerwerf, Jacobien J

Frontiers in immunology

2023 Volume 14, Page(s) 1208659

Abstract: This corrects the article DOI: 10.3389/fimmu.2023.980711.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2023.980711.].
Language	English
Publishing date	2023-05-24
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1208659
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Article ; Online: The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.

Frontiers in immunology

2023 Volume 14, Page(s) 980711

Abstract: Background and objective: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of ... ...

Abstract	Background and objective: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs). Methods: This is a Results: The subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods. Conclusion: Vaccination with BCG in the afternoon offered better protection against SARS-CoV-2 infections than BCG vaccination in the morning in the first six months after vaccination.
MeSH term(s)	Aged ; Humans ; Middle Aged ; COVID-19 ; BCG Vaccine ; SARS-CoV-2 ; Circadian Rhythm ; Mycobacterium bovis ; Respiratory Tract Infections ; Vaccination
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.980711
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Article ; Online: Routine vaccination for influenza and pneumococcal disease and its effect on COVID-19 in a population of Dutch older adults.

Taks, Esther J M / Föhse, Konstantin / J C F M Moorlag, Simone / Hoogerwerf, Jacobien / van Crevel, Reinout / van Werkhoven, Cornelis H / Netea, Mihai G / Ten Oever, Jaap

Vaccine: X

2023 Volume 14, Page(s) 100344

Abstract: Objectives: Protective heterologous beneficial effects of vaccines have been reported, and in this study we aimed to assess the impact of routine pneumococcal and influenza vaccination on the incidence and symptom duration of COVID-19 in a population of ...

Abstract	Objectives: Protective heterologous beneficial effects of vaccines have been reported, and in this study we aimed to assess the impact of routine pneumococcal and influenza vaccination on the incidence and symptom duration of COVID-19 in a population of Dutch older adults. Methods: This cohort study is a secondary analysis of the BCG-CORONA-ELDERLY study, a randomised controlled trial on the effect of BCG vaccination on the cumulative incidence of respiratory tract infections requiring medical intervention in adults ≥60 years. The primary outcome was the cumulative incidence of a self-reported positive SARS-CoV-2 PCR test, and was assessed using a Fine-Gray competing risks model adjusted for baseline characteristics at enrolment. We analysed data from November 1st 2020 until the end of the main study in May 2021. Results: Routine vaccination data 2020/2021 were available for 1963/2014 (97.5 %) participants; 44/1963 (2.2 %) were excluded due to COVID-19 before vaccination. 1076/1919 (56.1 %) had received the influenza vaccine and 289/1919 (15.1 %) the pneumococcal vaccine. The cumulative incidence of COVID-19 was 0.030 (95 %CI 0.021-0.041) in those vaccinated against influenza compared to 0.029 (95 %CI 0.019-0.041) in the unvaccinated group (subdistribution hazard ratio (SDHR) 1.018; 95 %CI 0.602-1.721). For pneumococcal vaccination the cumulative incidence was 0.031 (95 %CI 0.015-0.056) for the vaccinated and 0.029 (95 %CI 0.022-0.038) for non-vaccinated individuals (SDHR 0.961; 95 %CI 0.443-2.085). BCG vaccination in the previous year and sex were not significant effect modifiers in the primary analysis. Duration of fever, cough and dyspnoea was also not significantly different between treatment arms. Conclusion: Neither influenza nor pneumococcal vaccination was associated with a lower incidence or shorter duration of COVID-19 symptoms in older adults.
Language	English
Publishing date	2023-07-06
Publishing country	England
Document type	Journal Article
ISSN	2590-1362
ISSN (online)	2590-1362
DOI	10.1016/j.jvacx.2023.100344
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Article ; Online: Targeting the 16S rRNA Gene by Reverse Complement PCR Next-Generation Sequencing: Specific and Sensitive Detection and Identification of Microbes Directly in Clinical Samples.

Moorlag, Simone J C F M / Coolen, Jordy P M / van den Bosch, Bart / Jin, Elisabeth Hui-Mei / Buil, Jochem B / Wertheim, Heiman F L / Melchers, Willem J G

Microbiology spectrum

2023 Volume 11, Issue 3, Page(s) e0448322

Abstract: The detection and accurate identification of bacterial species in clinical samples are crucial for diagnosis and appropriate antibiotic treatment. To date, sequencing of the 16S rRNA gene has been widely used as a complementary molecular approach when ... ...

Abstract	The detection and accurate identification of bacterial species in clinical samples are crucial for diagnosis and appropriate antibiotic treatment. To date, sequencing of the 16S rRNA gene has been widely used as a complementary molecular approach when identification by culture fails. The accuracy and sensitivity of this method are highly affected by the selection of the 16S rRNA gene region targeted. In this study, we assessed the clinical utility of 16S rRNA reverse complement PCR (16S RC-PCR), a novel method based on next-generation sequencing (NGS), for the identification of bacterial species. We investigated the performance of 16S RC-PCR on 11 bacterial isolates, 2 polymicrobial community samples, and 59 clinical samples from patients suspected of having a bacterial infection. The results were compared to culture results, if available, and to the results of Sanger sequencing of the 16S rRNA gene (16S Sanger sequencing). By 16S RC-PCR, all bacterial isolates were accurately identified to the species level. Furthermore, in culture-negative clinical samples, the rate of identification increased from 17.1% (7/41) to 46.3% (19/41) when comparing 16S Sanger sequencing to 16S RC-PCR. We conclude that the use of 16S RC-PCR in the clinical setting leads to an increased sensitivity of detection of bacterial pathogens, resulting in a higher number of diagnosed bacterial infections, and thereby can improve patient care.
MeSH term(s)	Humans ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; Sequence Analysis, DNA/methods ; Bacteria ; Bacterial Infections/microbiology ; Polymerase Chain Reaction/methods ; High-Throughput Nucleotide Sequencing/methods ; DNA, Bacterial/genetics
Chemical Substances	RNA, Ribosomal, 16S ; DNA, Bacterial
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04483-22
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Article ; Online: Common and distinct metabolomic markers related to immune aging in Western European and East African populations.

Bulut, Ozlem / Temba, Godfrey S / Koeken, Valerie A C M / Moorlag, Simone J C F M / de Bree, L Charlotte J / Mourits, Vera P / Kullaya, Vesla I / Jaeger, Martin / Qi, Cancan / Riksen, Niels P / Domínguez-Andrés, Jorge / Xu, Cheng-Jian / Joosten, Leo A B / Li, Yang / de Mast, Quirijn / Netea, Mihai G

Mechanisms of ageing and development

2024 Volume 218, Page(s) 111916

Abstract: In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how ... ...

Abstract	In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how immune responses change with age in healthy Dutch and Tanzanian individuals and identify common metabolites associated with an aged immune profile. We performed untargeted metabolomics from plasma to identify age-associated metabolites, and we correlated their concentrations with ex-vivo cytokine production by immune cells, DNA methylation-based epigenetic aging, and telomere length. Innate immune responses were impacted differently by age in Dutch and Tanzanian cohorts. Age-related decline in steroid hormone precursors common in both populations was associated with higher systemic inflammation and lower cytokine responses. Hippurate and 2-phenylacetamide, commonly more abundant in older individuals, were negatively correlated with cytokine responses and telomere length and positively correlated with epigenetic aging. Lastly, we identified several metabolites that might contribute to the stronger decline in innate immunity with age in Tanzanians. The shared metabolomic signatures of the two cohorts suggest common mechanisms of immune aging, revealing metabolites with potential contributions. These findings also reflect genetic or environmental effects on circulating metabolites that modulate immune responses.
MeSH term(s)	Aged ; Humans ; Aging ; Cytokines ; East African People ; European People ; Immunity, Innate ; Metabolome
Chemical Substances	Cytokines
Language	English
Publishing date	2024-02-14
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	183915-9
ISSN	1872-6216 ; 0047-6374
ISSN (online)	1872-6216
ISSN	0047-6374
DOI	10.1016/j.mad.2024.111916
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Article ; Online: The impact of Bacillus Calmette-Guérin vaccination on antibody response after COVID-19 vaccination.

Taks, Esther J M / Moorlag, Simone J C F M / Föhse, Konstantin / Simonetti, Elles / van der Gaast-de Jongh, Christa E / van Werkhoven, Cornelis H / Bonten, Marc J M / Oever, Jaap Ten / de Jonge, Marien I / van de Wijgert, Janneke H H M / Netea, Mihai G

iScience

2023 Volume 26, Issue 11, Page(s) 108062

Abstract: Earlier studies showed that BCG vaccination improves antibody responses of subsequent vaccinations. Similarly, in older volunteers we found an increased IgG receptor-binding domain (RBD) concentration after SARS-CoV-2 infection if they were recently ... ...

Abstract	Earlier studies showed that BCG vaccination improves antibody responses of subsequent vaccinations. Similarly, in older volunteers we found an increased IgG receptor-binding domain (RBD) concentration after SARS-CoV-2 infection if they were recently vaccinated with BCG. This study aims to assess the effect of BCG on the serum antibody concentrations induced by COVID-19 vaccination in a population of adults older than 60 years. Serum was collected from 1,555 participants of the BCG-CORONA-ELDERLY trial a year after BCG or placebo, and we analyzed the anti-SARS-CoV-2 antibody concentrations using a fluorescent-microsphere-based multiplex immunoassay. Individuals who received the full primary COVID-19 vaccination series before serum collection and did not test positive for SARS-CoV-2 between inclusion and serum collection were included in analyses (n = 945). We found that BCG vaccination before first COVID-19 vaccine (median 347 days [IQR 329-359]) did not significantly impact the IgG RBD concentration after COVID-19 vaccination in an older European population.
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108062
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Article ; Online: BCG vaccination induces innate immune memory in γδ T cells in humans.

Suen, Tsz K / Moorlag, Simone J C F M / Li, Wenchao / de Bree, L Charlotte J / Koeken, Valerie A C M / Mourits, Vera P / Dijkstra, Helga / Lemmers, Heidi / Bhat, Jaydeep / Xu, Cheng-Jian / Joosten, Leo A B / Schultze, Joachim L / Li, Yang / Placek, Katarzyna / Netea, Mihai G

Journal of leukocyte biology

2023 Volume 115, Issue 1, Page(s) 149–163

Abstract: Bacillus Calmette-Guérin vaccine is well known for inducing trained immunity in myeloid and natural killer cells, which can explain its cross-protective effect against heterologous infections. Although displaying functional characteristics of both ... ...

Abstract	Bacillus Calmette-Guérin vaccine is well known for inducing trained immunity in myeloid and natural killer cells, which can explain its cross-protective effect against heterologous infections. Although displaying functional characteristics of both adaptive and innate immunity, γδ T-cell memory has been only addressed in a pathogen-specific context. In this study, we aimed to determine whether human γδ T cells can mount trained immunity and therefore contribute to the cross-protective effect of the Bacillus Calmette-Guérin vaccine. We investigated in vivo induction of innate memory in γδ T cells by Bacillus Calmette-Guérin vaccination in healthy human volunteers by combining single-cell RNA sequencing technology with immune functional assays. The total number of γδ T cells and membrane markers of activation was not influenced by Bacillus Calmette-Guérin vaccination. In contrast, Bacillus Calmette-Guérin changed γδ T cells' transcriptional programs and increased their responsiveness to heterologous bacterial and fungal stimuli, including lipopolysaccharide and Candida albicans, as simultaneously characterized by higher tumor necrosis factor and interferon γ production, weeks after vaccination. Human γδ T cells in adults display the potential to develop a trained immunity phenotype after Bacillus Calmette-Guérin vaccination.
MeSH term(s)	Adult ; Humans ; BCG Vaccine ; Trained Immunity ; Interferon-gamma ; Mycobacterium bovis ; Immunity, Innate ; Vaccination
Chemical Substances	BCG Vaccine ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2023-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiad103
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