ArticleThe Journal of clinical investigation2020
Circadian rhythm influences induction of trained immunity by BCG vaccination.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07527247 (Using AS01 Adjuvant to Improve Immune Response in Older Adults Through Trained Immunity), which is not on this map. Cited by 79 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Using AS01 Adjuvant to Improve Immune Response in Older Adults Through Trained Immunity
Who cites it
79 citing papers in PubMed, 4 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review.Frontiers in immunology · 2025Pooled it
- Circadian Variation in the Response to Vaccination: A Systematic Review and Evidence Appraisal.Journal of biological rhythms · 2024Pooled it
- Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.ESMO open · 2024Pooled it
- Sufficient Sleep, Time of Vaccination, and Vaccine Efficacy: A Systematic Review of the Current Evidence and a Proposal for COVID-19 Vaccination.The Yale journal of biology and medicine · 2022Pooled it
- Effect of the time of day for vaccination on the immune response to Ebola Virus Disease vaccines: A modeling study from PREVAC randomized trial.PLoS neglected tropical diseases · 2026Trial
- Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination.Immunology letters · 2024Trial
- The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.Frontiers in immunology · 2023Trial
- BMAL1 in cardiovascular diseases: Molecular mechanisms, circadian regulation and translational perspectives (Review).Molecular medicine reports · 2026Review
- Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- Recent perspectives on macrophage memory: types, mechanisms, and characteristics in pulmonary diseases.Cell communication and signaling : CCS · 2026Review
- Impact of time-of-day on immune checkpoint inhibitor therapy in cancer patients: an up-to-date clinical review.Frontiers in immunology · 2026Review
- Circadian immunoregulation in cutaneous wound healing: from immune cell temporal heterogeneity to chronotherapeutic strategies.Frontiers in immunology · 2026Review
- Optimizing Nivolumab Efficacy: The Role of Dosing Time in Advanced Non-Small Cell Lung Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Timing of immune checkpoint blockade shapes anti-tumor immunity via a clock-dependent chemokine axis.bioRxiv : the preprint server for biology · 2025Article
- Diurnally-Regulated Corticosterone and Melatonin Inversely Control Endotoxin-Induced Acute Immune Responses.European journal of immunology · 2025Article
- Review
- Circadian Clock: A Regulator of Immunity in Autoimmune Diseases.Immunity, inflammation and disease · 2025Review
- Understanding and improving vaccine efficacy in older adults.Nature aging · 2025Review
- Infection-induced trained immunity: a twist in paradigm of innate host defense and generation of immunological memory.Infection and immunity · 2025Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUNDThe antituberculosis vaccine bacillus Calmette-Guérin (BCG) reduces overall infant mortality. Induction of innate immune memory, also termed trained immunity, contributes toward protection against heterologous infections. Since immune cells display oscillations in numbers and function throughout the day, we investigated the effect of BCG administration time on the induction of trained immunity.METHODSEighteen volunteers were vaccinated with BCG at 6 pm and compared with 36 age- and sex-matched volunteers vaccinated between 8 am and 9 am. Peripheral blood mononuclear cells were stimulated with Staphylococcus aureus and Mycobacterium tuberculosis before, as well as 2 weeks and 3 months after, BCG vaccination. Cytokine production was measured to assess the induction of trained immunity and adaptive responses, respectively. Additionally, the influence of vaccination time on induction of trained immunity was studied in an independent cohort of 302 individuals vaccinated between 8 am and 12 pm with BCG.RESULTSCompared with evening vaccination, morning vaccination elicited both a stronger trained immunity and adaptive immune phenotype. In a large cohort of 302 volunteers, early morning vaccination resulted in a superior cytokine production capacity compared with later morning. A cellular, rather than soluble, substrate of the circadian effect of BCG vaccination was demonstrated by the enhanced capacity to induce trained immunity in vitro in morning- compared with evening-isolated monocytes.CONCLUSIONSBCG vaccination in the morning induces stronger trained immunity and adaptive responses compared with evening vaccination. Future studies should take vaccine administration time into account when studying specific and nonspecific effects of vaccines; early morning should be the preferred moment of BCG administration.FUNDINGThe Netherlands Organization for Scientific Research, the European Research Council, and the Danish National Research Foundation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.