Mon, 04 Jun 2018
The Pig Site speaks to Dr Bryan Charleston, viral immunology researcher at The Pirbright Institute for preventing and controlling viral diseases, about the most recent, game-changing breakthrough in swine immunology
Last week, it was announced that immunology scientists from a number of British research institutions have made a breakthrough in swine immunology that has been over 20 years in the making. The Pig Site spoke to Dr Bryan Charleston to learn more about what this advancement in swine immunology entails and how it will benefit the pig industry for the foreseeable future.
The key thing is that, for the last 20-30 years of studying the immune response in pigs, we’ve only been able to study the antibody response in some detail. We haven’t had the tools available to look at the other side of the immune response – the cellular immune response, specifically, the killer T-cells.
So, to simplify, the immune response relies on the antibodies and killer T-cells. Until now, we’ve been unable to measure, precisely, the killer T-cell response. There’s a lot of pathogens – viruses and bacteria – where, in order to overcome them, we need to stimulate a strong T-cell response. This is probably true for African Swine Fever, PRRS and influenza.
We used influenza virus, both infection and vaccination, to develop these tools that we've been missing. We’ve found a way to measure these killer T-cell responses precisely. You can measure the total number of killer T-cells that a pig will produce in response to infection or vaccination but, until now, we weren’t able to pinpoint exactly how many of those killer T-cells were responding directly to that vaccine or that virus.
We can now pinpoint the total number of killer T-cells that are responding only to that specific infectious agent, and we can also measure this across any body compartment and tissues, including blood, lungs etc.
There’s two reasons why this is so important:
1) Now we can look at the efficacy of different vaccines and vaccine delivery systems by precisely measuring the size of the immune response, in the part of the body that the vaccine is targeted at. For example, to overcome an infection with influenza virus, we are likely to need a high killer T-cell response in the respiratory tract where the infection is. The tools we have now allow us to do this as they tell us exactly how many killer T-cells are attacking the influenza virus-infected cells in the lungs, by using different vaccination methods.
This could be important for a number of pig diseases where we don’t currently have vaccines or we don’t have very effective vaccines, as we can start to understand if there are better ways of driving killer T-cell responses. Some of the work we’ve done at Pirbright is that we’ve identified potential candidates for ASF vaccines, using this method of measuring killer T-cell responses and identifying which proteins of a virus will stimulate the most effective protective immune response.
What we have shown in the recent paper, is that by delivering influenza vaccine by aerosol, we get a much higher level of killer T-cell response – this is interesting for pig vaccination development but could also be interesting for humans as pigs are commonly used as a physiological model for human medicine. As you can imagine, completing aerosol vaccine studies in humans is quite difficult to do, so this is an important breakthrough for both swine and human diseases.
There is a lot of interest in the pig as a model for human vaccine development as it is physiologically similar and, though there are some minor differences, our immune systems are broadly similar. Pigs could prove invaluable to developing the principles of vaccination delivery systems, which could apply to a number of species, including humans.
2) What this new tool allows us to do, is identify which bits of the virus or bacteria the immune system is seeing/detecting. For example, which proteins in the ASF virus is the immune system sensing and which number of those huge number of proteins should we put into a vaccine. This also allows us to identify which proteins of the virus that the pig immune system is seeing to drive a killer T-cell response. That will be critical information for designing new, effective vaccines.
The Babraham pigs were developed at the Babraham Institute about 30 years ago and the reason we worked with them in our trials is because they are an inbred herd so are highly genetically identical. This means that blood and cells can be transplanted between individuals easily, without rejection, which is important to ensure that consistency of response between individuals to allow accurate and valid interpretation of the results. Using genetically identical candidates for vaccination trials allows reliable repeats. They don’t represent the genetics in the wider pig population but the principles determined from the inbred population can be applied to the outbred population.
People have been trying to get these tools together for over 20 years and this is a great collaboration between veterinary researchers, such as ourselves here at Pirbright and our colleagues at Bristol, and human immunology researchers in Cardiff and Oxford. We’ve been able to bring together the application of the knowledge and experience of these groups, and apply their research on human immunology, to pigs.
It is this synergy between human and veterinary research which has advanced pig immunology to where it is now.
We have now moved pig immunology up into the same level of detail that we’ve achieved with mouse and human immunology.
We’re hopeful and optimistic that we will develop better strategies to dealing with infectious diseases using the tools that we have now developed.
Dr Bryan Charleston joined The Pirbright Institute in 1994 and focused on studies of the immune response to viral infections in cattle. In addition, he provided advice and expertise on the design of infectious disease challenge models for a wide range of pathogens in important agricultural species. His research is focused on understanding the immune response to foot-and–mouth disease virus (FMDV) in cattle to develop novel vaccines.