Researchers at the Babraham Institute are working to identify which mechanisms of the immune system still work well and which elements are less effective when we age. In a study published in Immunology and Cell Biology, scientists from the Babraham Institute, working with collaborators at the Pirbright Institute and the University of Oxford, report an increased reliance on the non-antibody mediated arm of the immune system to provide disease protection in aged mice following vaccination with the Oxford-AstraZeneca COVID-19 (ChAdOx1 nCoV-19) vaccine.
Understanding the effects of age on the different components of the immune system allows vaccine development to be tailored towards ensuring an effective level of protection in older people.
After vaccination, different branches of the immune system spring into action to provide protection. One mode of attack is via antibodies, but the immediate war against infection is led by cells known as CD8+ ‘killer’ T cells. These recognise signals on the surface of infected cells and release cytotoxic molecules which kill the target cell.
The Oxford-AstraZeneca COVID-19 vaccine is an adenovirus-based vaccine which encodes the COVID-19 spike protein. It stimulates the generation of anti-spike protein antibodies to neutralise virus, and also spike-specific CD8+ T cell responses to directly kill infected cells. Vaccines such as this provide an extra layer of immune protection by compensating for situations where lower levels of antibodies are produced, such as in older people.
To study the effect of age on the production and characteristics of spike-specific CD8+ T cells the researchers gave one dose of the Oxford-AstraZeneca vaccine to younger adult (3 months old) and aged (22 months old) mice and performed analysis to track where spike-specific CD8+ T cells were found in the body, their numbers, persistence and phenotype.
Once activated CD8+ T cells undergo a duplication process so that a large population of cells is created that recognise the same signal and therefore react to the threat. Some of these cells go on to form memory T cells which provide long-term protection.
The researchers’ analysis showed the spike-specific CD8+ T cells are produced in similar numbers in old and young mice in response to the vaccine, whereas protection by antibodies is diminished with age.
Dr William Foster, a postdoc in the Linterman lab who led the research, explained: “We were surprised to find that the expansion of spike-specific CD8+ T cell population occurs effectively despite the various age-associated defects in T cell biology. Developing our understanding of the ability of different cells to respond to infection is key to being able to achieve optimum protection of older individuals through vaccination.”
Despite being produced in comparable numbers, the T cells themselves gain age-associated changes that may alter their function. Further detailed phenotypic analysis of CD8+ T cells from the aged mice allowed the researchers to characterise the cellular changes that distinguish these cells from those found in younger animals. They found that the T cells from aged mice had higher levels of markers of cellular exhaustion, indicating a potential loss of functional capacity and suggesting that approaches to reverse this exhaustion state might restore responsiveness and further boost immunity delivered by CD8+ T cells.
Dr Michelle Linterman, a group leader in the Immunology research programme at the Institute, concluded: “This study highlights that vaccines that stimulate T cell immunity are ideal for older people, because the protection provided by CD8+ T cells is needed in the context of the diminished antibody responses that occur in ageing.”
As we build a better picture of how the different branches of the immune system change with age, we will move closer to being able to find ways of boosting the protection offered by vaccination especially for older people who are at higher risk of serious health consequences following infections.
Foster, W.S., et al. (2023) ChAdOx1 nCoV-19 vaccination generates spike-specific CD8+ T cells in aged mice. Immunol Cell Biol.
Honor Pollard, Communications Officer, firstname.lastname@example.org
Illustration of a world map with countries filled with multi-coloured images of syringes used to represent vaccination as a world-wide strategy for securing health. Image: Shutterstock 1857556006.
Babraham Institute affiliated authors (in author order):
William Foster, postdoctoral researcher, Linterman lab
Sarah Ross, former Group LeaderHayley Sharpe, Group Leader, Signalling programmeArianne Richard, Group Leader, Immunology programmeMichelle Linterman, Group Leader, Immunology programme
This research was funded by the Biotechnology and Biological Sciences Research Council, the Lister Institute of Preventative Medicine, the EPSRC VaxHub, and Innovate UK.
Animal research statement
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used mice that were immunised by injection and then humanely killed to allow researchers to analyse immune cell numbers and use those to assess the animals’ immune response to vaccines.
Please follow the link for further details of our animal research and our animal welfare practices. http://www.babraham.ac.uk/about-us/animal-research
Video explainer by Dr William Foster on the findings of the paper
Dr Michelle Linterman receives funding to understand how age affects vaccine response
Exploring the effects of age on the immune response to Oxford’s COVID-19 vaccine
16 May 2023