How to make better vaccines for humans and animals
26 January 2012
Researchers at the Institute for Animal Health (IAH) and collaborators at the Jenner Institute, University of Oxford, have discovered why some vaccines are not as effective at stimulating an immune response as we would hope and have investigated ways in which improvements could be made.
A dendritic cell has ingested only a small amount of BCG vaccine, which will limit the immune response. Copyright: Institute for Animal Health
The research was led at IAH in Compton, Berkshire, by Dr Jayne Hope (who is now based at The Roslin Institute, University of Edinburgh), Dr Efrain Guzman and Dr Bryan Charleston. The work is published this week in the journal, Vaccine. The project is funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Dr Charleston said "We knew that sometimes even when we know a bacteria or virus well, it has been a struggle to make effective vaccines against certain diseases. We discovered that dendritic cells - a type of immune cell - are activated better by some vaccines than others.
"There are a lot of human and animal diseases that we would like better vaccines for but until now we haven't been able to find a good reason why, for example, the BCG vaccine against tuberculosis isn't always effective but the bovine herpes virus vaccine is extremely efficient at establishing long term immunity."
The study focussed on the BCG vaccine that has been used against tuberculosis in humans and animals and which is known to have variable efficacy, but this discovery is important for developing new vaccines against many different diseases caused by viruses as well as bacteria.
Dendritic cells are the master regulators of immune responses to vaccination and infection; they circulate through the body detecting foreign material and then stimulate immune responses. Indeed, dendritic cells are the target of a number of therapies in humans to treat infections or cancer. A Nobel Prize was awarded this year to Ralph Steinman and colleagues because of their work on these pivotal cells.
Dr Hope said "When we studied dendritic cells in the lab, we found that BCG vaccine, for example, is taken up by only a small number of these cells. This could provide one of the reasons why this vaccine is not always effective. We had an idea that we could improve this and other vaccines by finding a way to enhance the response of dendritic cells which are key in driving immunity."
Dr Guzman added "The good news is that we've potentially found ways to improve the efficiency of the response by targeting dendritic cells. This may be a good approach to improve the long term immunity gained by vaccination.
"We did some experiments where we took a part of the BCG vaccine that we know elicits a strong response and we introduced that part directly into the cells."
The next stage is to develop this method into a safe and reliable technique that can be used for vaccination of humans and animals.
Part of the reason dendritic cells are important is that we often vaccinate through skin and these cells respond to the vaccination and then migrate towards the lymph nodes where the cells involved in long term immunity are activated.
The team at IAH have enhanced the technique of collecting dendritic cells directly from the lymphatic system of cattle. This makes these experiments possible whilst reducing the numbers of animals taking part in the research and allow confirmation that the results seen in the laboratory also occur in the animal.
This research is published in Vaccine in the article entitled "Migratory sub-populations of afferent lymphatic dendritic cells differ in their interactions with Mycobacterium bovis Bacille Calmette Guerin" doi 10.1016/j.vaccine.2012.01.036 and copyright is (c) 2012 Elsevier Ltd. All rights reserved.
The Institute for Animal Health, which receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), is a world-leading centre of excellence for research into viruses of farm animals, principally cattle, poultry, sheep and pigs, plus horses, and viruses which spread from animals to humans. Our research extends from fundamental to applied research, from genes all the way through to animal populations. It is our belief that better control of viral diseases requires a greater understanding of how each virus causes disease, how the immune systems of the farm animals respond to infection, and how the viruses spread, including those distributed by insects and other arthropods. In this way we contribute to the development of smarter, more effective vaccines; develop more discriminatory, user-friendly diagnostics; provide diagnostic services; and give expert knowledge to guide policy makers and farmers.
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, and with an annual budget of around £445M, 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.
Nancy Mendoza, Institute for Animal Health
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