Researchers from The Pirbright Institute, University of Bristol, Cardiff University and University of Oxford have generated tools that allow scientists to understand a vital area of the pig immune system which was previously inaccessible.
The methods developed show how immune cells in pigs, called CD8 (killer) T cells, are recruited in large numbers in the lung after infection with influenza or aerosol vaccination. The tools can also be used to identify virus proteins that are recognised by the immune system, offering the potential to design more effective vaccines. The same methods can be applied to other important pig diseases such as foot-and-mouth disease and African swine fever.
The breakthrough research, described in PLOS Pathogens, used a unique line of Babraham inbred pigs to develop these novel tools for examining T cell responses against flu infection or vaccination. The study brings methods for studying these vital immune cells up to the same high standards that are available for humans and mice.
It will now be possible to track the number and location of T cells in pig blood and tissues during infection, which can help determine the ability of vaccines to induce T cell immunity. The methods also allow researchers to predict which proteins will be recognised by pig T cells, therefore providing valuable information for vaccine improvement or development.
T cells can provide protection against multiple strains of flu, but current vaccines are unable to activate them effectively. The tools in this study were successfully used to show that aerosol delivery of a candidate influenza vaccine is highly efficient in triggering T cell responses in the lung, which are essential for protection against respiratory diseases.
The Babraham pigs played a pivotal role in this research. The team at Bristol have worked with the Babraham pigs for many years and have demonstrated a very high level of genetic similarity between individuals and shown that this could be used in studies of transplantation.
More recently, in a paper published in HLA, Pirbright researchers have shown that Babraham pigs are almost identical in molecules that are vital for initiating T cell immune responses (MHC molecules). This reduces experimental differences between animals making the Babraham pigs a valuable model for studying infectious disease.
The Babraham pigs are now the only example of a large inbred pig breed, which are more closely related physiologically to commercial pigs and indeed humans than other miniature pig models. As a consequence they have great potential to play an important role in studying infectious diseases in pigs, and as a preclinical model for human disease.
Dr Elma Tchilian, head of the Mucosal Immunology group at Pirbright said: “This study will equip us to track T cells during infection and understand how best to vaccinate animals and humans to achieve powerful protective immune responses. Our tools fill a gap which previously hindered swine immunology research, and can now be used in the study of many diseases.”
Professor Andrew Sewell, lead author of the study said: “Pigs provide a very good model system for influenza virus infection. They can be infected with both human and bird flu in addition to swine flu and are known to act as important ‘mixing vessels’ for the creation of pandemic flu strains. The new tools we’ve developed in Cardiff will allow researchers at Pirbright, the Bristol Veterinary School and elsewhere to closely study pig T cell responses to influenza for the first time. The ultimate goal will be to create a vaccine that can be effective against all strains of flu in pigs, birds and humans.”
Mick Bailey, Professor of Comparative Immunology in Veterinary Pathology and Infection and Immunity at the Bristol Veterinary School and whose group provided the monoclonal antibodies used to characterise the Babraham T-cells, said “The Babraham pigs are now a unique resource for studying health and disease in pigs both as globally important agricultural species and as models for human disease.”
Alain Townsend, Professor of Molecular Immunology at the Weatherall Institute Oxford University said: “The new techniques developed by Andy Sewell and his colleagues showed that our vaccine candidate called S-FLU induced a strong T cell response in the lung of the Babraham pig after aerosol delivery. This is a very helpful extension to the equivalent results we obtained in mice, and provides a unique opportunity for defining the protective role of these cells in a large animal that may model human disease more faithfully.”
Note to editors:
Funding for this work was provided by Biotechnology and Biological Sciences Research Council, grants BB/H001085/1 and BB/L001330/1, Wellcome Trust, grants WT100327MA and WT095767, and a Diamond Light Source beam-time allocation grouping (BAG) grant.
About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
With an annual income of nearly £26.1 million from grants and commercial activity, and a total of £5 million strategic investment from BBSRC during 2016-2017, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
About The University of Bristol
The University of Bristol is ranked within the top 50 universities in the world (QS World University Rankings 2018); it is also ranked among the top five institutions in the UK for its research, according to new analysis of the Research Excellence Framework (REF) 2014; and is the 4th most targeted university by top UK employers.
The University was founded in 1876 and was granted its Royal Charter in 1909. It was the first university in England to admit women on the same basis as men.
The University is a major force in the economic, social and cultural life of Bristol and the region, but is also a significant player on the world stage. It has over 16,000 undergraduates and nearly 6,000 postgraduate students from more than 100 countries, and its research links span the globe.
About Cardiff University
Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research intensive universities. The 2014 Research Excellence Framework ranked the University 5th in the UK for research excellence. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, Professor Sir Martin Evans. Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise encompasses: the College of Arts, Humanities and Social Sciences; the College of Biomedical and Life Sciences; and the College of Physical Sciences and Engineering, along with a longstanding commitment to lifelong learning. Cardiff’s flagship Research Institutes are offering radical new approaches to pressing global problems. www.cardiff.ac.uk
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £469 million in world-class bioscience in 2016-17. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
More information about BBSRC, our science and our impact: www.bbsrc.ac.uk
More information about BBSRC strategically funded institutes: www.bbsrc.ac.uk/institutes