Journal
SEMINARS IN IMMUNOLOGY
Volume 39, Issue C, Pages 35-43Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2018.06.002
Keywords
Vaccines; Non-specific effects; Morbidity; Mortality; Heterologous protection; Trained immunity
Categories
Funding
- ERC Consolidator Grant [310372]
- Spinoza Grant of the Netherlands Organization for Scientific Research
- Danish national Research Foundation [DNRF108]
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Besides protection against specific microorganisms, vaccines can induce heterologous or non-specific effects (NSE). Epidemiological data suggest that vaccination with live-attenuated vaccines such as Bacillus Calmette-Guerin (BCG), measles vaccine, and oral polio vaccine results in increased overall childhood survival, and several of these observations have been confirmed in randomized trials. Immunological mechanisms mediating NSE include heterologous lymphocyte effects and induction of innate immune memory (trained immunity). Trained immunity induces long-term functional upregulation of innate immune cells through epigenetic and metabolic reprogramming. An overview of the epidemiological evidence of non-specific effects of vaccines and the latest insights regarding the biological mechanisms behind this phenomenon is presented, and future research priorities and potential implications are discussed.
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