During the development of the ChAdOx1 nCoV-19 vaccine by the Oxford Vaccine Group, immunologists at the Babraham Institute undertook a vital assessment of the effects of age on the vaccine’s performance. The research provides the cellular detail of the complex immune response and highlights differences in the immune response in young and aged mice.
The work is published online in Med, a new journal from Cell Press, and presents the research performed in partnership between researchers in the Linterman lab at the Institute – experts on the effects of age on immune system function – and the research team of Teresa Lambe who developed the ChAdOx1 nCoV-19 vaccine at the University of Oxford’s Jenner Institute.
The global SARS-CoV-2 pandemic has dominated worldwide news during 2020 and affected nearly every aspect of daily life. Since the emergence of the disease, one of the key questions has been about the development of an effective vaccine. Following significant announcements on vaccine efficacy and safety by Pfizer/BioNTech, Moderna and Oxford/AstraZeneca, the UK initiated a phased vaccination programme in the UK earlier this month. As part of this process, and with the prioritisation of older and vulnerable people, it is essential to know that any vaccine performs effectively in older people and protects those at most risk.
“As we get older, our immune system function declines and we become more vulnerable to infectious disease,” explains Dr Michelle Linterman, a Babraham Institute group leader and lead on the research study. “The current pandemic has highlighted how much of a health imbalance this can cause. This work has allowed us to analyse the immune system response to the vaccine at cellular resolution and learn more about how age affects this.”
The Institute team tested the vaccine ChAdOx1 nCoV-19 (AZD-1222) in aged mice. The average lifespan of a mouse is two years. The research used mice aged between three months (the mouse equivalent of the prime of life) and 22 months (the mouse equivalent of old age). Despite the fact that ageing in mice and humans happens on different timescales, many of the biological changes that occur in the immune system with age are seen in both mice and humans. Previous research using mice has also shown that strategies to boost immune responses in older mice are also effective in humans.
The Institute researchers found that although a single dose of the ChAdOx1 nCoV-19 vaccine was sufficient to trigger an immune system response in older mice, the response was reduced when compared to the vaccine response in younger adult mice. The research closely analysed the different immune cell types that form the body’s overall ‘surveillance’ system and the cells that specifically identify and kill infected cells.
Following the initial vaccination with a second booster dose one month later enhanced the immune response in older mice, overcoming the deficiency of the first response.
“Stimulating the production of long-lived antibodies is key to securing longer-term immunity,” said Dr Teresa Lambe, Associate Professor & Jenner Investigator, University of Oxford. “While the aged mice initially showed a compromised ability to produce these, a booster dose of the vaccine improved this response.”
The results of the Phase 2 trial of ChAdOx1 nCoV-19 were published in The Lancet on the 18th of November. As with the mouse results, the clinical trial data shows that the vaccine is effective at stimulating a strong antibody and T cell immune response across all age groups, including older people, after two doses of the vaccine. Data from a pooled analysis of Phase 3 trials was released on 8th December. Due to only a small number of participants being over 55 years old, it was not possible to assess the vaccination efficiency in older ager groups using this data. The University of Oxford reported that this will be assessed in future analyses as more data from this age group is returned.
Silva-Cayetano, A., Foster, W.S. & Innocentin, S. et al. A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice. Med. DOI:https://doi.org/10.1016/j.medj.2020.12.006 Published 15 December 2020.
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About the ChAdOx1 nCoV-19 clinical trials
See the information on coronavirus research at the University of Oxford: Oxford ChAdOx1 nCoV-19 clinical trials and press announcements on their Oxford vaccine trial website.
Confocal microscopy image of the spleen nine days after ChAdOx1 nCoV-19 immunisation in an aged mouse (22 months old). The image shows immunofluorescence staining to identify different classes of immune cell: IgD+ B cell follicle in green, CD3+ T cells in magenta, Ki67+ proliferating cells in blue and CD35+ follicular dendritic cells in white. Image: Sigrid Fra-Bido, Babraham Institute.
Affiliated authors (in author order):
Alyssa Silva-Cayetano, postdoctoral researcher, Linterman lab
William Foster, postdoctoral researcher, Linterman lab
Silvia Innocentin, research assistant, Linterman labOliver Burton, senior postdoctoral researcher, Liston lab
Sigrid Fra-Bidó, research assistant, Linterman lab
Jia Le Lee, PhD student, Linterman lab
Nicola Evans-Bailey, animal unit supervisor, animal facility
Carly Noble, animal facility manager, animal facilityAdrian Liston, group leader, Immunology research programmeMichelle Linterman, group leader, Immunology research programme
This study was supported by strategic funding to the Institute from the Biotechnology and Biological Sciences Research Council, and funding from the Lister institute of Preventative Medicine, the EPSRC VaxHub and Innovate UK. Michelle Linterman is an EMBO Young Investigator and a Lister Institute Prize Fellow. Jia Le Lee is supported by a National Science Scholarship (PhD) by the Agency for Science, Technology and Research, Singapore.
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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 in vaccination studies. Mice were vaccinated and humanely killed at various timepoints post vaccination to provide tissue and blood for analysis.
All mouse experimentation was approved by the Babraham Institute Animal Welfare and Ethical Review Body. Animal husbandry and experimentation complied with existing European Union and United Kingdom Home Office 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 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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16 December 2020