Final Report: Professor Lorna Harries and Merlin Davies – Developing a new animal-free tool to detect Covid-19

  • This project was made up of two parts focusing on COVID-19:
    1. The first study developed an animal free COVID-19 PCR test which determined how the amount of active virus in a patient sample linked to the severity of symptoms.
    2. The second study focused on changes in immune cell activity and antibody production in older patients with COVID-19. Drugs were then tested to see if they could improve immune cell responses.
  • A repurposed cancer drug was found to improve immune responses in older people.
  • This was one of the first studies of its kind to use only animal-free antibodies.
  • Some of the results were published in the International Journal of Infectious Diseases, and another paper is currently being written.
  • The work was reported on in national and international media outlets including The Independent, I, Times and Telegraph.
  • The work will be presented at the British Society of Immunology annual conference, a field which is particularly reluctant to switch to animal-free antibodies.
Merlin Davies - animal Free Research UK

PhD Student Merlin Davies

The infection risk of COVID-19

COVID-19 is a disease caused by a virus named SARS-CoV-2. First discovered in December 2019, the infection is highly contagious and quickly spread around the world. Following the peak of the pandemic and easing of lockdown restrictions, the uncertainty around how long someone remained infectious after contracting the virus impacted people needing to return to work and daily life. Furthermore, those requiring medical treatment such as patients awaiting bone marrow transplants, and who needed a definitive negative test first, experienced delays in treatment.

Current routine testing for COVID-19 measures viral fragments, which are parts of the virus that have been shed. As these fragments can be infectious or non-infectious, people can test positive for long periods but may or may not be an infection risk to others. To make testing more accurate, measuring a person’s viral load instead (which is a direct measure of the amount of active virus in the body), could be a more effective way to assess how infectious a person is.

Developing an animal-free COVID-19 test

Merlin Davies, a PhD student worked alongside Professor Lorna Harries, at the University of Exeter’s Animal Free Research Centre of Excellence (ARC 2.0) to develop a new test measuring the viral load of SARS-CoV-2 genetic material in a patient’s nasopharyngeal swab sample (mucus samples taken from the top of the throat).

Current COVID-19 tests include ingredients derived from animals, so Merlin and his team modified the test to make it free from animal ingredients for use in their experiments. This test was then used to detect the amount of active virus in a patient’s sample and find out how this linked to the severity of the patient’s symptoms.

The SARS-CoV-2 virus that causes COVID-19

The SARS-CoV-2 virus that causes COVID-19

Using leftover nasopharyngeal samples from patients and healthcare workers who tested positive for COVID-19, Merlin found that patients with higher amounts of viral load had more severe symptoms. He also found that the higher the level of viral load, the longer a person is potentially infectious, with a third of patients still infectious after 5 days and 13% still infectious after 10 days. As lockdown restrictions allowed people to return to work after 5 days of isolation and two negative lateral flow tests, this meant there could be a risk of disease spread that was dangerous for older and clinically vulnerable people.

This research led to the publication of a paper and was also reported in regional and national newspapers including The Independent during the pandemic.

Finding a link between patient age and immune response

The second part of Merlin’s project focused on how well our immune cells (the cells in our body which fight infection) work, and how efficiently older patients with COVID-19 produce antibodies to fight the virus. The study compared immune cells taken from healthy adults over 60 to those taken from people aged 18-35, to find out if a person’s age affects their immune response to SARS-CoV-2 infection.

Merlin Davies - animal Free Research UK

Merlin Davies working on developing an animal-free COVID-19 test to measure viral load.

Merlin found that older people’s immune cells react differently to those of younger people when faced with the SARS-CoV-2 virus. Older people’s immune cells were found to create both lower numbers and different types of defensive antibodies when exposed to the virus, meaning that their ability to fight the virus is lower. This provides an opportunity to specifically target drugs (known as senotherapeutic drugs) towards older cells, to improve and strengthen the patient’s immune response.

A cancer drug was repurposed to test this effect on a small number of patient immune cell samples, and preliminary results showed a stronger antibody response, compared to that seen in the younger cells. With further testing, these drugs could help improve the immune responses of older people to SARS-CoV-2 infection. The repurposing of an already approved drug also avoids the need for further lengthy drug development and associated animal testing, bringing benefits for both people and animals.

This type of research usually uses antibodies which are produced in animals, and over 1 million animals are used in antibody production each year in Europe alone. Excitingly, this study was one of the first of its kind to be carried out using only animal-free antibodies. The group hope that this will pave the way for future studies to be carried out using similar animal-free reagents, potentially saving the lives of thousands of animals.

The impact of this research

This project has achieved several important outcomes and has opened doors to exciting future avenues of work, including the repurposing of drugs which have already been approved for other diseases to improve immune responses in older people.

This project also reinforces the fact that immunological research, which often includes animal-derived biomaterials and animal experiments, can be successfully conducted in an entirely animal free manner.

Some of the results from Merlin’s project have already been published in the International Journal of Infectious Diseases, and another paper is currently being written. The work will also be presented at future conferences including the British Society of Immunology annual conference.

A further important take away from this project is that there are lots of differences in the way that each human individual’s immune systems work, and this is also affected by our age. Animals therefore are not an accurate or reliable way of reflecting what happens in viral responses in people. Moving away from animal-derived biomaterials and towards a more human-specific approach will lead to benefits for people sooner.