Top Jabs - Improving vaccination responses in older adults

Lead Research Organisation: University of Birmingham
Department Name: Immunity and Infection

Abstract

Older adults are more likely to get infections than young people, which is why the NHS vaccinates against the ?flu and pneumonia because of immune system ageing. Unfortunately, as people age, their body?s immune system works less well, meaning that responses to vaccination are less able to protect against illness. It is important to better understand why older people have poorer vaccine responses and to improve these. We plan to research this in older animals and humans. We will look at the processes involved in making high quality antibodies in mice, and test three ways of improving the vaccination response in mice and humans ? adding to vaccine components; improving people?s sensitivity to insulin; or simply changing the time of day when vaccines are given.

Technical Summary

Older adults are more susceptible to bacterial and viral infections than young people and the national vaccination programmes against influenza and Streptococcus pneumonia are the primary preventive measure aimed at reducing incidence of these infections. However, the decline in immune function in old age reduces the ability of older individuals to mount successful vaccination responses, with less than half of over 65 year olds producing a protective response to influenza. With age both the quantity and quality of antibody produced is reduced, which will reduce the efficacy of vaccination in older adults. Many older adults are therefore not benefitting from the protection provided by vaccination. There is an urgent need to understand why the vaccination response is compromised in old age and to develop interventions to improve vaccination responses in elders.
We plan to address several aspects of the immune response to vaccination in older animals and humans to determine why there is a failure to develop good humoral immune responses in older adults. T cell memory and B cell differentiation are directed by adult lymphoid tissue inducer (LTi) cells. We will test if and how their reduced function impacts on reduced antibody responses in old age. In addition, immune complexes have been used as adjuvants in old mice, and we will study how antigen-masking changes selection and affinity maturation of B lymphocytes in lymphoid tissues in older animals. Crucially, we will test whether antigen-masking can be used as an efficient and novel vaccine adjuvant in older animals.
Age related hormonal and metabolic changes also contribute to reduced immune responses. The study will test whether insulin sensitivity is related to vaccination responses, and will test in a small pilot study in animals whether a pharmacological intervention (metformin treatment) can improve vaccine response. Finally, a simple behavioural intervention will be used to modulate efficiency of vaccination responses: Our preliminary data show that diurnal variations in older adults lead to changes in the quality of humoral vaccine responses. We will repeat this in a larger randomised trial and test whether diurnal changes in responsiveness are due to variations in stress hormones or cytokines. If proved effective, this observation will lead to a simple intervention by manipulating the timing of immunization to improve the response to vaccination in older adults.

Publications

10 25 50

 
Description AgeWell annual research days
Amount £15,000 (GBP)
Organisation University of Birmingham 
Department Medawar Centre for Healthy Ageing Research
Sector Academic/University
Country United Kingdom
Start 09/2011 
End 10/2013
 
Description AgeWell annual research days continued
Amount £15,000 (GBP)
Organisation Versus Arthritis 
Department Arthritis Research UK Centre for Musculoskeletal Ageing Research
Sector Academic/University
Country United Kingdom
Start 09/2014 
End 10/2017
 
Description Biomedical Vacation Scholarships
Amount £1,080 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2013 
End 06/2013
 
Description Determining the potential universal applicability of a diurnal response to vaccination and the associated circadian immune processes
Amount £550,130 (GBP)
Funding ID MR/P001874/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2017 
End 12/2019
 
Description Horizon 2020 Marie Curie Multi-site International Training Network
Amount € 2,873,941 (EUR)
Funding ID [675003] 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2016 
End 12/2020
 
Description MRC Centenary award
Amount £8,655 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2012 
End 04/2013
 
Description MRC Centenary award
Amount £5,900 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 11/2012 
End 04/2013
 
Description MRC Centres Capital Awards
Amount £254,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2013 
End 04/2014
 
Description MRC Confidence in Concept, Design and preclinical testing of a cancer specific vaccine
Amount £67,212 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2013 
End 04/2014
 
Description MRC DPFS, Specific targeting of a pro-inflammatory B cell subset in rheumatoid arthritis
Amount £591,471 (GBP)
Funding ID MR/M007669/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2014 
End 06/2017
 
Description Project grant Effects of IL-22 deficiency on germinal centre physiology
Amount $437,000 (USD)
Organisation Pfizer Inc 
Sector Private
Country United States
Start 11/2011 
End 11/2013
 
Description Project grant How does systemic flagellin immunization induce mucosal IgA
Amount £654,061 (GBP)
Funding ID BB/L009986/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2014 
End 03/2017
 
Description Public Involvement Fund for patient participant involvement in planned NIHR funded clinical trial
Amount £350 (GBP)
Organisation Research Design Service, West Midlands 
Sector Public
Country United Kingdom
Start 01/2016 
End 07/2016
 
Title monoclonal antibody NP-specific 
Description Several hybridomas producing monoclonal antibodies with defined specificities to 4-hydroxynitrophenyl (NP) have been made, which can be used to study regulation of antibody responses to NP. 
Type Of Material Antibody 
Year Produced 2013 
Provided To Others? Yes  
Impact These tools allow study of antibody feedback in the regulation of B cell selection in germinal centres 
 
Description Gene expression in memory B cells 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of mRNA from in vivo differentiated memory B cells
Collaborator Contribution Gene expression analysis from different in vivo differentiated memory B cells by RNAseq and bioinformatic analysis
Impact New data on gene expression in new memory B cell subsets.
Start Year 2015
 
Description In silico modelling of germinal centres 
Organisation Helmholtz Association of German Research Centres
Department Helmholtz Centre for Infection Research (HZI)
Country Germany 
Sector Academic/University 
PI Contribution Data provision for in silico models Work on the in silico model
Collaborator Contribution In silico modelling Predictions for optimal experimental in vivo setups
Impact The collaboration has led to several publications. It has produced a new in silico model to analyse the regulation of affinity maturation in germinal centres. This has lead to several further collaborations and publications for our collaborators.
Start Year 2006
 
Description Intravital imaging of memory B cell migration 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of GMO mice,
Collaborator Contribution Immunisation of GMO mice and intravital imaging of migrating memory B cells. Training visits for UoB staff on intravital microscopy in preparation.
Impact Early results show new patterns of memory B cell migration and roles of chemokine receptors directing this.
Start Year 2016
 
Description Intravital imaging of plasma cell differentiation 
Organisation Leibniz Association
Department German Rheumatism Research Centre
Country Germany 
Sector Charity/Non Profit 
PI Contribution A postdoctoral research fellow spent twice 2 months at DRFZ to learn intravital imaging techniques and study plasma cell differentiation from germinal centres
Collaborator Contribution Hosting, training, and help with experiments. Provision of experimental animals
Impact Training of postdoctoral research fellow Preliminary data on plasma cell differentiation Submission of funding proposal to Wellcome Trust for an intravital microscope
Start Year 2011
 
Title CONJUGATED VACCINE 
Description The present invention provides a composition for provoking an immune response in a patient to an autoantigen target, the composition comprising the target conjugated a carrier polypeptide. 
IP Reference US2016136287 
Protection Patent granted
Year Protection Granted 2016
Licensed No
Impact None yet
 
Title Tumour endothelium targeting B cell vaccine 
Description We have developed a vaccine that induces antibody to tumour vessel expressed antigens, inhibiting tumour growth. This has been tested and developed in mice. Translation to a human version has started. At the moment further funding is sought. Last source of funding was MRC CiC. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2014
Development Status Actively seeking support
Impact The vaccine design should be applicable for other targets, e.g. other tumour expressed antigens, or other autoantigens involved in the pathogenesis of other diseases. 
 
Description Interactive presentation and poster at Lifelong Health and Wellbeing Public Showcase, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact About 150 members of the public attended this interactive display and discussion session

Many questions were asked about how to boost immunity
Year(s) Of Engagement Activity 2012
 
Description Invited talk and display for NDA and LLHW joint Public Engagement Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 100 older adults and practitioners attended the talks and interactive presentation which sparked questions and discussion

The public asked about the best time to have vaccinations for best immune protection
Year(s) Of Engagement Activity 2013
 
Description Levels of antibodies in saliva are associated with risk of mortality. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Levels of antibodies in saliva are associated with risk of mortality. Media engagement, e.g., the Times, Daily Mail, Huffington Post, Science Daily etc.
Year(s) Of Engagement Activity 2015
URL http://www.sciencedaily.com/releases/2015/12/151223221330.htm
 
Description Loneliness and isolation, can it affect your immunity? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact Loneliness and isolation, can it affect your immunity? Speaker at Dudley Age Alliance - Public engagement for older adults and practitioner, charities and health care providers
Year(s) Of Engagement Activity 2015
 
Description Loneliness and isolation, can it affect your immunity? Speaker at Dudley Age Alliance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Loneliness and isolation, can it affect your immunity? Speaker at Dudley Age Alliance - Public engagement for older adults. Invited by a member of the Birmingham 1000 elders cohort which was revamped at the original AgeWell meeting funded by this grant.
Year(s) Of Engagement Activity 2015
 
Description Morning vaccination is better for older adults. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Morning vaccination is better for older adults. Radio and TV Interviews for Naked Scientist and BBC World News, plus lots of other media nationally and globally e.g. the Guardian, NY Times, BBC Health, the Telegraph, Reuters, Huffington Post, Radio WM, O Globo, Times of India
Year(s) Of Engagement Activity 2016
URL http://www.birmingham.ac.uk/news/latest/2016/04/vaccinations-more-effective-in-the-morning.aspx
 
Description Museum activity day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Schools
Results and Impact Visitors to Birmingham's science museum (ThinkTank) could meet scientists and learn about the immune system. Hundreds of children and their parents talked to us and engaged in activities.

Children learnt about the immune system, and had a chance to meet scientists. Many were very enthused about science and experiments. We were invited back for this year and intend to return next year.
Year(s) Of Engagement Activity 2012,2013
 
Description Poster and interactive display at the Lifelong Health and Wellbeing Showcase event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 100 members of the public attended an interactive poster session on ageing research at which we presented our work

Many members of the public asked about when the best time was for their influenza vaccination
Year(s) Of Engagement Activity 2013
 
Description School visits 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact We ran experiments with the whole of year 6, talked about being a scientist and answered all their questions about what we did.

The children learnt that they could be scientists and that not all scientists were old white men with beards and glasses! The school invited us back to talk to the children in 2014.
Year(s) Of Engagement Activity 2012,2013
 
Description Speaker at Bright Club - Public engagement with Science event. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Speaker at Bright Club - Public engagement with Science event. Comedy presentation of science
Year(s) Of Engagement Activity 2015
URL https://www.youtube.com/watch?v=bK2BNCguX8w