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 is led by scientists at the Rosalind Franklin Institute. The research was funded by 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 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, it 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:
The team found three nanobody chains 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:
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:
Source: UK Research and Innovation.
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