The Humane Research Trust is funding a research project to develop an animal-free ex vivo model of the human tonsil to test vaccines with. By applying 3D cell culture techniques to donated human tonsil tissue, the University of Glasgow researchers will create a platform for studying human immune responses. Using the measles vaccine, the scientists will prove their approach could replace animal testing in the preclinical stages of vaccine development.
Developing new vaccines is a long and complex process, involving many stages of extensive testing. Pharmaceutical scientists must estimate the likely effectiveness of candidate vaccines before they test them in humans. This usually involves immunising live animals with the vaccine to assess how their immune systems respond to it. The problem is that these studies often don’t replicate the human immune response.
“Currently, the translation of fundamental research into vaccine effectiveness is highly inefficient,” explains Professor Margaret Hosie, Professor of Comparative Virology at the University of Glasgow. “Many vaccine candidates that show early promise in animal models subsequently prove ineffective in clinical trials.”
Another challenge in the field is the emergence of zoonotic diseases – infectious diseases that can jump from animals to humans. Existing vaccines, such as the measles-mumps-rubella (MMR) vaccine provide a degree of cross-protection from related zoonoses. However, as diseases such as measles come close to eradication, experts are concerned that the requirement for this vaccine would cease. This could leave humans susceptible to infection with related animal-borne diseases.
Thus, there is a growing need to develop better ways to study immune responses to vaccines, both existing and new. Scientists are turning to new tools and technologies to help them develop more biologically relevant ways of carrying out this kind of research.
One alternative to animal testing involves creating ‘organoids’ – lab-grown collections of human cells – which can then be used for testing. There are various ways to do this – one method involves repurposing tonsil tissue, usually discarded after a patient’s tonsillectomy. Following exposure to a virus or vaccine candidate, the organoids reproduce the natural immune response of the tissue’s donor.
Tonsil organoid systems are particularly useful for vaccine development because tonsils produce antibody-secreting cells called plasmablasts, which multiply and present antigens (substances which trigger immune responses). As a result, tonsil models can enable scientists to study the early stages of immunity and identify specific antibodies that can effectively target viruses.
The Humane Research Trust is currently funding a research project at the University of Glasgow to develop and apply a new tonsil organoid system. Led by Prof Hosie, the scientists will use tissue samples from a range of donors to develop organoids. This will enable them to evaluate the impact of characteristics like sex, age, ethnicity and vaccine history on immune response.
Once they have developed their model, they will use it to test the MMR vaccine. This will prove that we can efficiently study the effects of novel vaccines without the need for animal models. Additionally, they’ll uncover key insights about how the MMR vaccine protects humans from related animal-borne diseases.
Earlier tonsil models have relied on an animal-derived product called foetal bovine serum to support the growth of the organoids. This serum is made from the bodies of unborn cows. Prof Hosie’s laboratory will replace this product with a synthetic alternative, making the model entirely animal-free and therefore more relevant to humans.
“This model system has enormous potential to replace the use of animals in the development of novel vaccines and therapeutics,” explains Prof Hosie. “Our goal is to further our understanding of the diversity of human immune responses to infection and vaccination. This would improve the rationale for which candidates should be selected for clinical trial, leading to improved and accelerated vaccine design.”
Prof Margaret Hosie
Principal investigator
Prof Hosie is a Professor of Comparative Virology at the University of Glasgow. Her laboratory's role is to research how infectious diseases develop, develop diagnostic tools, and identify new vaccines that can prevent them. Feline immunodeficiency virus - a virus affecting cats that is similar to the human lentivirus (HIV) - has been a major focus of Prof Hosie's work.
Lee Sherry
Postdoctoral researcher
Lee is a Postdoctoral Research Associate at the University of Glasgow. His work in molecular virology has focused on understanding the characteristics of viruses that lead to disease and optimising virus-like particles' ability to induce immune responses. The goal of his work is to produce better vaccine candidates.
