Non-specific effects of vaccines: Current evidence and potential implications

Semin Immunol. 2018 Oct;39:35-43. doi: 10.1016/j.smim.2018.06.002. Epub 2018 Jul 11.


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-Guérin (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.

Keywords: Heterologous protection; Morbidity; Mortality; Non-specific effects; Trained immunity; Vaccines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • BCG Vaccine / administration & dosage
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / immunology*
  • Child
  • Epigenesis, Genetic
  • Humans
  • Immunity, Heterologous*
  • Immunity, Innate / drug effects*
  • Immunologic Memory / drug effects*
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Measles Vaccine / administration & dosage
  • Poliovirus Vaccines / administration & dosage
  • Randomized Controlled Trials as Topic
  • Sex Factors
  • Vaccination*


  • BCG Vaccine
  • Measles Vaccine
  • Poliovirus Vaccines