ArticleProceedings of the National Academy of Sciences of the United States of America2012
Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 10 registered trials, which are not on this map. Cited by 990 papers, 3 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.
The Effects of BCG-vaccination on the Innate Immune Response in Healthy Volunteers. Pilot Proof-of-principle Studie
Bacillus Calmette-Guerin Vaccination as Defense Against SARS-CoV-2: A Randomized Controlled Trial to Protect Health Care Workers by Enhanced Trained Immune Responses
Performance Evaluation of BCG Vaccination in Healthcare Personnel to Reduce the Severity of SARS-COV-2 Infection in Medellín, Colombia, 2020
Reducing Morbidity and Mortality in Health Care Workers Exposed to SARS-CoV-2 by Enhancing Non-specific Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial
Randomized Trial Evaluating the Non-specific Effects of Different BCG Strains in Guinea-Bissau: Effects on Early-life Mortality and Morbidity
Bacillus Calmette-Guerin Against Covid-19 for Prevention and Amelioration of Severity Trial
Novel Use of an Existing Vaccine (BCG) Alliance: The NUEVA Trial
Prevention of Acute Respiratory Infection in Taiwanese Institutionalized Elderly (PARITIE)
Diabetes Diagnosis, Management, Prevention and Education in Guinea-Bissau
Using AS01 Adjuvant to Improve Immune Response in Older Adults Through Trained Immunity
Who cites it
990 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,674 citations in OpenAlex.
- Preclinical Evaluation of Bacterial Lysates in Murine Disease Models: A Systematic Review.Immunity, inflammation and disease · 2026Pooled it
- Mucosal immunity and vaccine development.Signal transduction and targeted therapy · 2026Pooled it
- Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review.Frontiers in immunology · 2025Pooled it
- BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection.Open forum infectious diseases · 2025Trial
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- The origin of non-specific effects of vaccines and the role of randomised clinical trials.Human vaccines & immunotherapeutics · 2026Review
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Trained Immunity in Childhood Vaccination.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- The epigenetic-metabolic axis of trained immunity: dual roles in disease pathogenesis and intervention.Journal of molecular medicine (Berlin, Germany) · 2026Review
- The epigenetic-metabolic axis of trained immunity: dual roles in disease pathogenesis and intervention.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection.Science advances · 2026Article
- Maturation-Dependent Constraints in the Ability of Human Monocytes to Initiate Trained Immunity.MedComm · 2026Article
- Monocyte-derived galectin-1Nature immunology · 2026Article
- Anisotropic Masked Mycobacterium Potentiates Amplified Antitumor Trained Immunity via Spleen Targeting and Myelopoiesis Conversion.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- COVID-19 mRNA Vaccines as Antigen-Agnostic Immunomodulators: A Repurposing Perspective.Medical sciences (Basel, Switzerland) · 2026Review
- Drugging trained immunity: immunometabolic and epigenetic control of maladaptive inflammatory memory in chronic inflammatory diseases.Immunologic research · 2026Review
- Review
- No Association of Prior Administration of Selected Vaccines with Lymphoma Prognosis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- The theory of the inflammatory ecosystem.Science China. Life sciences · 2026Review
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 2026Review
930 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Adaptive features of innate immunity, recently described as "trained immunity," have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of circulating monocytes persisted for at least 3 mo after vaccination and was accompanied by increased expression of activation markers such as CD11b and Toll-like receptor 4. These training effects were induced through the NOD2 receptor and mediated by increased histone 3 lysine 4 trimethylation. In experimental studies, BCG vaccination induced T- and B-lymphocyte-independent protection of severe combined immunodeficiency SCID mice from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in control mice). In conclusion, BCG induces trained immunity and nonspecific protection from infections through epigenetic reprogramming of innate immune cells.
Indexed as
Identifiers
What OpenQuestion holds
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.