04/11/2021
Key points:
We are currently witnessing the ability of vaccination programmes to limit the burden of infectious disease on both individuals and society. Despite their success, most vaccines are not completely effective, and efficacy varies significantly due to individual immune response but also age and other factors. Understanding the cellular and molecular interactions that lead to a strong immune response is key to improving vaccines. Research published this week in eLife by Dr Michelle Linterman and her team assessed multiple aspects of the vaccination response following a 'flu vaccine and identified age-related differences where the vaccine stimulated pro-inflammatory signalling which affects cells key to developing a strong immune response. This study suggests that interventions to dampen inflammation at the time of vaccination may boost immune responses in older people.
As we get older, our immune response to vaccination becomes weaker, and researchers are still trying to understand why. Dr Linterman and her lab looked for an explanation by comparing over 50 different immune variables in individuals before and after vaccination, including the level of neutralising antibodies raised to the protein the ‘flu virus uses to enter cells (haemagglutinin), cell signalling molecules and B and T cell responses. The researchers were able to track the immune cells that responded to the vaccination to be certain that the changes they were seeing were a result of the vaccine.
The team found that the number of circulating T follicular helper cells (cTfh) that specifically recognise the influenza protein haemagglutinin were the best indicator for a strong immune response and that these cells differentiate from pre-existing memory cells, but that in older people this differentiation process is reduced.
Looking for an explanation for impaired cTfh cell differentiation in older people, the researchers investigated the transcriptome to detect differences in the genes expressed in the vaccine-specific cTfh cells from younger and older individuals. They found that cells from older individuals failed to acquire the full gene signature seen in Tfh cells from younger people. Moreover, they detected the activation of pro-inflammatory signalling pathways in cTfh cells from older people in response to vaccination, which negatively impacts an optimal vaccine response.
Dr Linterman said: “Understanding the molecular events behind our body's response to vaccination shows us what is happening when the immune response isn't as strong as it could be. Our research provides a proof of concept that enhanced inflammation is a feature of the vaccination response in older people and that this limits the formation of T follicular helper cells, which are in turn essential for supporting good antibody production. This suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people.”
Publication reference Hill, D. et al. Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans, eLife 2021;10:e70554
Press contact Honor Pollard, Communications Officer, honor.pollard@babraham.ac.uk
Image description: Tfh cells (green) within a germinal centre. Credit: Ine Vanderleyden, Babraham Institute
Affiliated authors (in author order): Danika Hill, former postdoc, Linterman lab Carly Whyte, former postdoc Silvia Innocentin, Research assistant, Linterman lab Jia Le Lee, PhD student, Linterman lab James Dooley, Senior staff scientist, Liston lab Adrian Liston, Senior group leader, Immunology research programme Edward Carr, former postdoc, Linterman lab Michelle Linterman, Group leader, Immunology research programme, and an EMBO Young Investigator and Lister Institute Prize Fellow
Research funding This study was supported by H2020 European Research Council, the Biotechnology and Biological Sciences Research Council, the National Health and Medical Research Council Australia, and the Wellcome Trust.
Additional/related resources: Linterman research group page News 1 May 2021 Babraham Institute scientists find clues to explain reduced vaccine response with age News 16 December 2020: Exploring the effects of age on the immune response to Oxford’s COVID-19 vaccine
Animal research statement: As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. Animals are only used in Babraham Institute research when their use is essential to address a specific scientific goal, which cannot be studied through other means. The research presented here used mice in vaccination studies. The mice were bred and maintained in the Babraham Institute Biological Support Unit. Mice were infected with influenza A virus under anaesthesia and then immunised. In a separate procedure, mice were injected with immune cells. Animal husbandry and experimentation complied with existing European Union and national legislation and local standards.
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About the Babraham Institute The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
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04 November 2021