Report

Teaser, summary, work performed and final results

Periodic Reporting for period 3 - TWILIGHT (ToWards Immunisations that Last: the Immunology and Gerontology of Helper T cells)

Teaser

One of the major achievements of the modern era is the extension of the human life-span through improvements in medical care, nutrition, sanitation and access to clean water. The consequent shift towards older populations creates a challenge for society, not least for medical...

Summary

One of the major achievements of the modern era is the extension of the human life-span through improvements in medical care, nutrition, sanitation and access to clean water. The consequent shift towards older populations creates a challenge for society, not least for medical science: how to enable people to age in good health and remain active throughout their lives. Ageing is accompanied by a functional decline of the immune system, resulting in an increased overall susceptibility to infections that are a major cause of morbidity and mortality in older people. Development of strategies to mitigate or overcome these changes remains one of the major challenges of healthy ageing. One of the most successful medical interventions for preventing infectious disease has been vaccination. However, age-related changes in the immune system mean that older individuals often do not generate protective immunity after vaccination. This leads to an increased prevalence of preventable disease in older people, even with good immunisation programmes in place. Therefore, improving vaccine efficacy in older individuals is a key scientific challenge that, if met, would enable all of us to be healthier and more active throughout our lives. Most vaccines provide protection by generating antibodies that block the ability of a pathogen to establish an infection. However, antibody production after vaccination is diminished in older persons. This project aims to understand the age-dependent changes in the immune system that result in poor antibody production after vaccination.

Work performed

- We have characterised vaccine responses in younger and older individuals, and determined which changes associate with poor antibody responses.
- We have shown that follicular regulatory T cells can derive from Foxp3- precursors, and be specific for the immunising antigen.
- In human vaccination studies we have identified a population of circulating follicular regulatory T cells that act as a peripheral biomarker of this cell type
- We have shown that age is one of the biggest drivers of variation in the human immune system

Final results

Improving vaccine efficacy is key to reducing infection-related morbidity in older people. To date, the complexity of the ageing process has hindered attempts to fulfil this ambition, and thus innovative approaches are required to better understand the underlying biology. This project utilises research on mice and humans to combine the tractability advantages of mice with the physiological relevance of studying humans. This will ensure that this research programme delivers mechanistic insight into a complex biological problem that is relevant to healthy ageing in humans.