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Understanding and improving vaccine efficacy in older adults

Nature Aging volume 5, pages 1455–1470 (2025)Cite this article

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Abstract

Cellular aging of the immune system, commonly referred to as ‘immunosenescence’, drives a substantial decline in vaccine efficacy among older adults, who are already typically at a higher risk of reduced infection control. Therefore, preventive medicine requires novel strategies to improve vaccination in older adults, particularly by finding ways to mitigate immunosenescence and chronic inflammation. Here, we review how technical innovations, such as increased antigen amounts, improved adjuvants and mRNA-based and universal vaccines, can complement traditional methods of improving vaccination success in older adults. Furthermore, we discuss emerging clinical evidence suggesting that geroscience interventions, such as mTOR inhibition and caloric restriction, can enhance vaccine outcomes in older adults, potentially by targeting molecular aspects of immunosenescence and systemic characteristics of aging, including metabolic changes in the blood and chronic inflammation. Ultimately, we propose that integrating geroscience with tailored immunization could attenuate the effects of immune aging on vaccination efficacy in older populations.

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Fig. 1: Multilevel drivers of impaired vaccine efficacy in older adults.
Fig. 2: Putative cellular targets and effects of geroprotective interventions tested in vaccine studies.
Fig. 3: Exploring new approaches to using personalized medicine, geroscience and vaccine development to address age-related vaccine inefficacy.

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Acknowledgements

P.K. is funded by the Wellcome Trust (222426/Z/21/Z), a Medical Research Council IMMPROVE Proactive Vaccinology grant and Cancer Research UK (DRCNPG-Nov22/100005). A.K.S. is supported by the Wellcome Trust Fund 220784/Z/20/Z and the Helmholtz Distinguished Professorship.

Author information

Authors and Affiliations

  1. Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany

    Sebastian J. Hofer, Simon Rapp & Anna Katharina Simon

  2. Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK

    Paul Klenerman

  3. National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

    Paul Klenerman

  4. Peter Medawar Building for Pathogen Research and Pandemic Sciences Institute, University of Oxford, Oxford, UK

    Paul Klenerman

  5. Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK

    Anna Katharina Simon

Authors
  1. Sebastian J. Hofer
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  2. Simon Rapp
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  3. Paul Klenerman
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  4. Anna Katharina Simon
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Contributions

S.J.H. and A.K.S. conceptualized the review. All authors contributed to writing and editing the paper.

Corresponding author

Correspondence to Sebastian J. Hofer.

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Competing interests

A.K.S. has received consultancy fees from TLL The Longevity Labs GmbH, Oxford Healthspan and Kalin Health. P.K. has received consulting fees from UCB, Biomunex, AstraZeneca and Infinitopes. S.J.H. and S.R. declare no competing interests.

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Nature Aging thanks Jorg Goronzy, Sean Leng and the other anonymous, reviewer(s) for their contribution to the peer review of this work.

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Hofer, S.J., Rapp, S., Klenerman, P. et al. Understanding and improving vaccine efficacy in older adults. Nat Aging 5, 1455–1470 (2025). https://doi.org/10.1038/s43587-025-00939-6

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