A unique antibody produced by llamas could be developed as a new frontline treatment against COVID-19 and could be taken by patients as a simple nasal spray.
The laboratory research was led by scientists at the Rosalind Franklin Institute and funded by the UK Research and Innovation’s (UKRI) Medical Research Council (MRC), the Engineering and Physical Sciences Research Council (EPSRC), the EPA Cephalosporin Fund, and Wellcome.
Using nanobodies to target the virus
The research has shown that nanobodies (a smaller, simple form of antibody generated by llamas and camels) can effectively target the SARS-CoV-2 virus that causes COVID-19.
It is the first step towards developing a new type of treatment against COVID-19. The scientists are hoping to progress this work from the animal setting to prepare for clinical studies in humans.
The research team found that short chains of the molecules, which can be produced in large quantities in the laboratory, significantly reduced signs of the COVID-19 disease. It can be administered either nasally or by injection to infected animal models.
The nanobodies bind tightly to the SARS-CoV-2 virus, neutralising it in cell culture. They could ultimately provide a cheaper and easier to use alternative to human antibodies taken from patients who have recovered from COVID-19.
Human antibodies have been an important treatment for serious cases during the pandemic, but typically need to be administered by infusion through a needle in a hospital.
Testing the new treatment
The research team published their findings in the journal Nature Communication. They were able to generate the nanobodies by injecting a portion of the SARS-CoV-2 spike protein into a llama called Fifi, who is part of the antibody production facility at the University of Reading.
The spike protein is found on the outside of the virus and is responsible for binding to human cells so it can infect them.
Although the injections did not make Fifi sick, they triggered her immune system to fight off the virus protein by generating nanobodies against it. A small blood sample was then taken from the llama and the researchers were able to purify four nanobodies capable of binding to the COVID-19 virus.
The nanobodies were then combined into chains of three to increase their ability to bind to the virus. These were then produced in cells in the laboratory.
Examining the nanobody structure
Professor James Naismith, Director of the Rosalind Franklin Institute, who helped lead the research, said: “Because we can see every atom of the nanobody bound to the spike, we understand what makes these agents so special.”
The team found three nanobody chains that were able to neutralise both the original variants of the COVID-19 virus and the Alpha variant that was first identified in Kent, UK. A fourth nanobody chain was able to neutralise the Beta variant first identified in South Africa.
When one of the nanobody chains (also known as a trimer) was administered nasally to hamsters infected with SARS-CoV-2, the animals showed a marked reduction in disease. They lost far less weight after seven days than those who remained untreated.
Hamsters that received the nanobody treatment also had a lower viral load in their lungs and airways after seven days than untreated animals.
Adapting to fight diseases
Professor Ray Owens, Head of Protein Production at the Rosalind Franklin Institute and lead author of the research, said: “Nanobodies have a number of potential advantages over human antibodies.
“They are cheaper to produce, and it is possible to deliver them directly to the airways through a nebuliser or nasal spray, so they could be self-administered at home rather than needing an injection.
“This could have benefits in terms of ease of use by patients, but it also gets the treatment directly to the site of infection in the respiratory tract.”
The researchers also hope the nanobody technology they have developed could form a so-called ‘platform technology’ that can be rapidly adapted to fight other diseases.
Dr Andrew Bourne, Director of Partnerships at EPSRC, said: “Utilising the unique properties of llamas’ nanobodies, this research could lead to an important new form of treatment for COVID-19 that is cheaper to produce and easier to administer.”
It is a vivid illustration of the impact that long-term discovery research at the cutting edge of physical and life sciences can have, as undertaken at the Rosalind Franklin Institute, which has been further accelerated through UKRI agile funding.