SPECIALTY TOPICS · GUIDE
Trained Immunity
What trained immunity (innate immune memory) means, the BCG vaccine evidence in children and adults, and why the idea does not support supplements or products sold to train your immune system.
Content last updated . This page has not been medically reviewed.
Back to Emerging Wellness ScienceWhat it is
A 2020 review defines trained immunity as a de facto innate immune memory: activation of the innate immune system can result in enhanced responsiveness to subsequent triggers. [1] Researchers describe it as driven by epigenetic reprogramming, meaning sustained changes in gene expression and cell behavior without permanent changes to the DNA sequence. [2] The same review notes benefits for host defense but also potentially harmful outcomes in immune-mediated and chronic inflammatory diseases. [1]A nephrology review adds that both circulating cells and immune progenitor cells in the bone marrow may be trained, which could explain long-term protective effects of vaccination against unrelated infections. [3] It also reports that inappropriately induced trained immunity may contribute to aberrant inflammation, for example in lupus and systemic sclerosis, and has been associated with acute rejection in organ transplantation. [3] Trained immunity is therefore a mechanism with possible upsides and downsides, not a "boost".
The best-studied example: BCG vaccine
The BCG vaccine is the usual example for the "non-specific effects" idea. Results differ by age and by outcome.| Evidence | What it found |
|---|---|
| Systematic review, children under 5 (34 birth cohorts) [4] | BCG was associated with lower all-cause mortality: relative risk 0.70 (95% CI 0.49 to 1.01) from five trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. |
| BRACE trial, adults (6,828 healthcare workers; 12-month secondary outcomes) [5] | Risk of at least one febrile or respiratory illness was 66.8% with BCG and 63.4% with control, a small increase of 3.4 percentage points (95% CI 1.3 to 5.5); no difference in severe illness. |
| Danish trial, healthcare workers (1,221; BCG vs placebo) [6] | No significant effect on unplanned absenteeism or COVID-19 incidence overall; in a secondary analysis, revaccination was associated with higher COVID-19 incidence (hazard ratio 2.47, 95% CI 1.07 to 5.71) and lower hospitalization (0.28, 0.09 to 0.86). |
| Meta-analysis of 12 randomized trials for COVID-19 (18,086 participants) [7] | No significant difference in COVID-19 infection (pooled risk ratio 1.02, 95% CI 0.91 to 1.14) or in severity measures. |
How to read the table: the childhood findings come mostly from observational studies and short trials, and the observational studies were at high risk of bias. [4] The adult trials, which are randomized and larger, did not show protection against respiratory or COVID-19 illness, and the largest found a small increase in mild illness. [5][7] BRACE's funders included philanthropic foundations. [5]
Label: non-specific protection by BCG in children is mixed, mostly observational; in adults against respiratory infection, the randomized evidence read here is no good evidence of benefit. This does not say anything about BCG's role against tuberculosis, which this page did not examine.
Why this does not support "train your immune system" products
- A laboratory finding that a substance changes innate cell responses is preclinical or biomarker-level evidence. A biomarker change is not a clinical outcome. See laboratory immune effects vs clinical benefit.
- The research reviewed here used a vaccine given in clinical studies and in a clinical setting. None of it addresses supplements, mushroom extracts, cold exposure or other practices. Practical options are covered by herbs and mushrooms for immunity and supporting immune health.
- Because trained immunity is reported to have possible harmful effects in inflammatory disease, enhancing it is not automatically desirable. [1][3]
Frequently asked questions
What is trained immunity?
It is the idea that the innate immune system can show enhanced responsiveness to later triggers after an initial activation, a sort of innate memory. [1]
Does the BCG vaccine protect against COVID-19 or colds?
Randomized evidence read for this page does not show protection. A meta-analysis of 12 trials found no significant difference in COVID-19 infection, and a large trial found slightly more febrile or respiratory illness in the BCG group over 12 months. [7][5]
Is trained immunity always good?
No. Reviews describe possible contributions to chronic inflammatory disease, lupus, systemic sclerosis and transplant rejection. [1][3]
Can a supplement or diet train my immune system?
The sources read for this page address a vaccine only. They do not show that any supplement, food or practice produces trained immunity with a health benefit.
Where is the research heading?
Reviews suggest it may inform new vaccine approaches and treatments for immune deficiency or exaggerated inflammation, but that is a hypothesis, not a result. [2]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Safety and who should talk to a clinician
References
- Defining trained immunity and its role in health and disease. Nat Rev Immunol 2020. Read 2026-10-22.
- Trained immunity: A program of innate immune memory in health and disease. Science 2016. Read 2026-10-22.
- Trained immunity - basic concepts and contributions to immunopathology. Nat Rev Nephrol 2022. Read 2026-10-22.
- Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ 2016. Read 2026-10-22.
- Bacille Calmette-Guerin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial. EClinicalMedicine 2026. Read 2026-10-22.
- Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial. J Infect Dis 2024. Read 2026-10-22.
- Efficacy of BCG vaccination against COVID-19 in health care workers and non-health care workers: a meta-analysis of randomized controlled trials. PLoS One 2025. Read 2026-10-22.