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

Charlotte L.C.J. de Bree; Valerie A.C.M. Koeken; Leo A.B. Joosten; Peter Aaby; Christine Stabell Benn; Reinout van Crevel; Mihai G. Netea

doi:10.1016/j.smim.2018.06.002

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

Charlotte L.C.J. de Bree
, Valerie A.C.M. Koeken
, Leo A.B. Joosten
, Peter Aaby
, Christine Stabell Benn
, Reinout van Crevel
, Mihai G. Netea^*

^*Corresponding author for this work

KI, OUH, Research Unit OPEN (Odense)

Radboud University Medical Center
University of Bonn
Statens Serum Institut

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

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.

Original language	English
Journal	Seminars in Immunology
Volume	39
Pages (from-to)	35-43
ISSN	1044-5323
DOIs	https://doi.org/10.1016/j.smim.2018.06.002
Publication status	Published - Oct 2018

Funding

MGN was supported by an ERC Consolidator Grant ( #310372 ) and a Spinoza Grant of the Netherlands Organization for Scientific Research . CVIVA is supported by a grant from the Danish national Research Foundation ( DNRF108 ).

Keywords

Heterologous protection
Morbidity
Mortality
Non-specific effects
Trained immunity
Vaccines

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10.1016/j.smim.2018.06.002

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title = "Non-specific effects of vaccines: Current evidence and potential implications",

abstract = "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-Gu{\'e}rin (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",

author = "\{de Bree\}, \{Charlotte L.C.J.\} and Koeken, \{Valerie A.C.M.\} and Joosten, \{Leo A.B.\} and Peter Aaby and Benn, \{Christine Stabell\} and \{van Crevel\}, Reinout and Netea, \{Mihai G.\}",

year = "2018",

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doi = "10.1016/j.smim.2018.06.002",

language = "English",

volume = "39",

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T1 - Non-specific effects of vaccines

T2 - Current evidence and potential implications

AU - de Bree, Charlotte L.C.J.

AU - Koeken, Valerie A.C.M.

AU - Joosten, Leo A.B.

AU - Aaby, Peter

AU - Benn, Christine Stabell

AU - van Crevel, Reinout

AU - Netea, Mihai G.

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

KW - Heterologous protection

KW - Morbidity

KW - Mortality

KW - Non-specific effects

KW - Trained immunity

KW - Vaccines

U2 - 10.1016/j.smim.2018.06.002

DO - 10.1016/j.smim.2018.06.002

M3 - Journal article

C2 - 30007489

AN - SCOPUS:85049622486

SN - 1044-5323

VL - 39

SP - 35

EP - 43

JO - Seminars in Immunology

JF - Seminars in Immunology

ER -

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

Abstract

Funding

Keywords

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