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Review
. 2021 Jul 27;6(1):93.
doi: 10.1038/s41541-021-00354-z.

Vaccination as a preventative measure contributing to immune fitness

Béatrice Laupèze  1 , Giuseppe Del Giudice  2 , Mark T Doherty  3 , Robbert Van der Most  4
Affiliations
Review

Vaccination as a preventative measure contributing to immune fitness

Béatrice Laupèze et al. NPJ Vaccines. .

Abstract

The primary goal of vaccination is the prevention of pathogen-specific infection. The indirect consequences may include maintenance of homeostasis through prevention of infection-induced complications; trained immunity that re-programs innate cells to respond more efficiently to later, unrelated threats; slowing or reversing immune senescence by altering the epigenetic clock, and leveraging the pool of memory B and T cells to improve responses to new infections. Vaccines may exploit the plasticity of the immune system to drive longer-term immune responses that promote health at a broader level than just the prevention of single, specific infections. In this perspective, we discuss the concept of "immune fitness" and how to potentially build a resilient immune system that could contribute to better health. We argue that vaccines may contribute positively to immune fitness in ways that are only beginning to be understood, and that life-course vaccination is a fundamental tool for achieving healthy aging.

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Conflict of interest statement

All authors are employed by and hold shares in the GSK group of companies and do not have any non-financial relationships and activities to declare.

Figures

Fig. 1
Fig. 1. Changes in the immune system with age.
Summary of key changes in the immune system with age.
Fig. 2
Fig. 2. Healthy lifestyle pyramid adapted from Philip et al.
Life-course immunization as a key component of a healthy lifestyle pyramid.
Fig. 3
Fig. 3. Possible immunological mechanisms explaining downstream effects of vaccination (adapted from Benn 2013).
After vaccination for pathogen X two possible pathways may explain downstream effects: A Epigenetic re-programming of monocytes/macrophages leading to a more rapid activation after exposure to pathogen Y, to ensure rapid clearance of this pathogen. B T cell-mediated cross-reactivity: memory CD4 and CD8 T cells are generated that are cross-reactive with pathogen Y. PRR pattern recognition receptors, MHC major histocompatibility complex, TLR Toll-like receptors, CLR C-type lectin receptors, TCR T cell receptor.
Fig. 4
Fig. 4. Intrinsic and extrinsic modulators of immune fitness.
Intrinsic and extrinsic modulators may either challenge or strengthen the immune system. External challenges can result in either A the loss in immune system homeostasis (unhealthy state) in the absence of intrinsic capabilities or B the maintenance of homeostasis in the presence of intrinsic capabilities (healthy state). Vaccination may potentially have a positive influence through trained immunity, by creating a flexible memory pool, by direct and indirect prevention of diseases triggered by infections and associated inflammation.
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