On 1 December 2025, Professor Dame Sarah Gilbert will be presenting the 88th Stephen Paget Memorial lecture, “Development of vaccines against outbreak pathogens”.
The Stephen Paget Memorial Lecture
The Stephen Paget Memorial Lecture is a scientific lecture that commemorates the life of Dr Stephen Paget. Stephen Paget (185 –1926) was the founder of the Research Defence Society, a forerunner of Understanding Animal Research. As a medical doctor, he believed passionately that better science and understanding of physiology would lead to better medical treatments.
You can read and watch nearly a hundred years of lectures on animalresearch.info.
Professor Dame Sarah Gilbert
From pathogens to vaccines
Famed for her work on the Oxford–AstraZeneca Covid-19 vaccine which was rapidly produced and supplied in huge quantities to countries worldwide during the 2020 pandemic, Professor Dame Sarah Gilbert has directed her career towards tackling emerging viral pathogens. “I've always been very interested in understanding how biological systems work and then using that to change things and make things better. I get the chance to do that now,” she explains.
First interested in the genetics of host parasite interactions in malaria, her work led to an understanding of how to develop a vaccine against the parasite.
Malaria parasites are quite elusive. There's a particular stage of the malaria lifecycle that can't be attacked by antibodies (the first line of immune defence) inside the human body, but it can be targeted by another part of the immune system known as T cells. As part of Prof Adrian Hill’s group, Prof Gilbert worked on vaccines that used viral vectors – similar to the one she developed to fight Covid-19 – because unlike conventional vaccination techniques which tend to trigger only an antibody response, these also induce a T cell specific immune response.
This was a turning point for researchers. From malaria, she moved to working on viral vector based pandemic flu vaccines, anticipating the possibility of an animal-to-human outbreak. “That got me into the pandemic outbreak pathogens field,” she says. It is a field on which she has left an indelible mark.
From one pandemic to the next
In 2014, the largest outbreak of Ebola virus the world had ever seen occurred in West Africa. As the disease spread, Prof Gilbert was asked to help in testing an adenoviral-vector vaccine, produced by one of her collaborators in Italy. Very quickly clinical trials were run in Oxford and Mali with promising results.
“Disappointingly that vaccine never made it into efficacy trials because there were a lot of delays and concerns about what to do next,” she explains. “The whole response to the Ebola outbreak in 2014 was recognised very widely as a failure. The world was not prepared to deal with it. Systems weren't ready. Vaccines weren't ready. That led to a change in the way we think about these disease outbreaks. Since then, the WHO and other organisations, have created their lists of priority pathogens that have caused outbreaks, and continue to cause outbreaks, but for which we don't have vaccines, diagnostics, or therapeutics. The Coalition for Epidemic Preparedness and Innovation (CEPI) was formed to fund vaccine development.”
Prof Gilbert was the Oxford lead on the bid to CEPI’s first call for proposals, which aimed to develop vaccines against MERS, Nipah and Lassa viruses. When the SARS-CoV-2 coronavirus broke out, she had already been working on a MERS coronavirus vaccine. She had tested it in animals and validated it in two clinical trials. At the beginning of 2020, there was enormous pressure for fast results. Prof Gilbert replicated the design of the MERS vaccine and tested to see if it produced an immune response in mice. Immunisation and challenge studies in non-human primates followed, after which the Covid-19 vaccine clinical trials in humans began. “Because of my previous work, I knew what vaccine design would result in a good, strong, and protective immune response. We got vaccine development underway very rapidly,” she says.
Since then, Prof Gilbert has built a taskforce against outbreak pathogens. “We have the capacity to move relatively quickly from designing a new vaccine to in-house manufacturing, getting it tested in animal and clinical trials. Our ultimate aim is to have tested vaccines and stockpiles of vaccines against the pathogens that we know will continue to cause outbreaks, so that, in the event of one, we'll be able to respond much more quickly.”
How animals fit in the vaccine development process
Today, as an experienced vaccinologist, Prof Gilbert is very aware that her work would not have been possible without studies in animals: “Animal research is essential, but we are always looking for opportunities to reduce the number of animals used, whether that is through very careful experimental design or statistical optimisation. There is an increased focus on using human organoids to test vaccines and look at immune responses, but these are not fully ready to replace animals in the research we conduct. Animals are still very much needed.”
Animals are used at different stages of the vaccine development process. First and foremost, they are used in basic immunological tests. They help researchers make sure a vaccine induces an immune response correctly and to define which version of a vaccine performs best before it goes into clinical trials. Usually, these tests are run in mice.
Efficacy testing can occur in other animal species, depending on the pathogen. Most emergent pathogens come from animals and evolve to infect humans. It is often possible to test if a vaccine works in the source animal. For instance, a Nipah vaccine can be tested in pigs, the original carrier of the disease. In other cases, such as with the MERS coronavirus or the SARS-CoV-2 that causes Covid-19, a small number of non-human primates can be used for efficacy studies. They are used to assess whether the immune response induced by a vaccine can protect them against infection. Animals are exposed to the virus while in a containment facility to see if they are protected from the disease. There are a few pathogens for which these types of challenge studies can be safely conducted in humans, but these remain exceptions.
Vaccines can also be designed for animals directly, to prevent infection in humans. If the animal is protected from the disease, it will be less likely to spread to humans. In this case, we are not just testing the vaccine in animals, we are aiming to protect the animals against the disease because that, in turn, protects us.
Last edited: 1 December 2025 10:42
