Maintaining a ‘fit’ immune system: the role of vaccines

ABSTRACT

Introduction

Conventionally, vaccines are thought to induce a specific immune response directed against a target pathogen. Long recognized but poorly understood nonspecific benefits of vaccination, such as reduced susceptibility to unrelated diseases or cancer, are now being investigated and may be due in part to “trained immunity’.

Areas covered

We discuss ‘trained immunity’ and whether vaccine-induced ‘trained immunity’ could be leveraged to prevent morbidity due to a broader range of causes.

Expert opinion

The prevention of infection i.e. maintaining homeostasis by preventing the primary infection and resulting secondary illnesses, is the pivotal strategy used to direct vaccine design and may have long-term, positive impacts on health at all ages. In the future, we anticipate that vaccine design will change to not only prevent the target infection (or related infections) but to generate positive modifications to the immune response that could prevent a wider range of infections and potentially reduce the impact of immunological changes associated with aging. Despite changing demographics, adult vaccination has not always been prioritized. However, the SARS-CoV-2 pandemic has demonstrated that adult vaccination can flourish given the right circumstances, demonstrating that harnessing the potential benefits of life-course vaccination is achievable for all.

Graphical Abstract

KEYWORDS:

• Immune fitness
• epigenetics
• innate immunity
• aging
• inflammaging
• vaccination

Article highlights

• Non-specific effects of vaccines on unrelated diseases, including other infections and cancer, have been postulated since at least the early 20^th century.

• These non-specific effects may be due in part to epigenetic reprogramming of innate immune cells, leading to ‘“trained immunity”’.

• Vaccination induces an immunological stimulus and some vaccines (eg BCG) induce ‘trained immunity’ alongside specific immune responses. As a result, myeloid cells show enhanced production of pro-inflammatory cytokines and provide protection against unrelated pathogens that can last for a year or longer after vaccination.

• By preventing infection, vaccines may contribute to good health and immune fitness by helping to maintain immune homeostasis.

• As yet, the deliberate use of targeted vaccine-induced ‘trained immunity’ for wider disease prevention remains speculative. Nonetheless, along with lifestyle factors such as diet and exercise, vaccination has an unambiguous role in promoting good health and immune fitness.

Box: glossary

Bioage: biological age measured by several available tools that aim to predict health and remaining healthy lifespan and life expectancy

Epigenetics: modifications to gene expression brought about by altered access to transcription factors, promoter regions, silencer regions, through acetylation, methylation, or phosphorylation of histones.

Histones: structural proteins that wrap DNA within the nucleus and play a role in regulating gene expression by ‘opening’ or ‘closing’ wound DNA structures, allowing increased/decreased access to transcription factors.

Immune biography: the overall immune responsiveness that arises as the sum of all of the immune encounters experienced throughout a lifetime

Immune fitness: a resilient immune system capable of adapting to external challenges by employing an appropriate immune response and returning to baseline or near baseline levels of activation.

Immunosenesence: age-related, progressive modulation of immune system functioning, often associated with gradually developing chronic inflammation.

‘Trained immunity’: re-programming of innate immune cells that causes them to respond differently to immune activation by acquiring a form of immune memory

Acknowledgments

The authors thank Business & Decision Life Sciences platform for editorial assistance and publication coordination, on behalf of GSK. Joanne Wolter (independent medical writer on behalf of GSK) for providing medical writing support.

Declaration of interest

Béatrice Laupèze and T. Mark Doherty are employed by and hold shares in GSK. GSK have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors participated in the discussion and the development of this manuscript, reviewed and approved the final manuscript.

Additional information

Funding

GlaxoSmithKline Biologicals SA funded all costs associated with the development and publishing of the present manuscript.