Harnessing the beneficial heterologous effects of vaccination

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Clinical evidence strongly suggests that certain live vaccines, in particular bacille Calmette–Guérin (BCG) and measles vaccines, can reduce all-cause mortality, most probably through protection against non-targeted pathogens in addition to the targeted pathogen. The underlying mechanisms are currently unknown. We discuss how heterologous lymphocyte activation and innate immune memory could promote protection beyond the intended target pathogen and consider how vaccinologists could leverage heterologous immunity to improve outcomes in vulnerable populations, in particular the very young and the elderly.

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Figure 1: Heterologous lymphocyte responses.
Figure 2: Mechanisms of innate memory in monocytes and macrophages.


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This work was supported by funding from the US National Institutes of Health (NIH) Infant Immunity Program (RO1 5R01AI100135-03 to O.L.), the European Research Council (Consolidator Grant 310372 to M.G.N.), the Michael Smith Foundation for Health Research (Career Investigator Award to T.R.K.), the Canadian Institute of Health Research (300819 to T.R.K.), the British Columbia Children's Hospital Foundation (to T.R.K.), and the NIHR Oxford Biomedical Research Centre (to A.J.P.).

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Correspondence to Helen S. Goodridge.

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Goodridge, H., Ahmed, S., Curtis, N. et al. Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol 16, 392–400 (2016) doi:10.1038/nri.2016.43

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