Llama Nanobodies Effective at Preventing and Treating COVID-19

Llama Nanobodies Effective at Preventing and Treating COVID-19

SARS-CoV-2 vaccines have significantly reduced the number of deaths from COVID-19, but the virus remains a major threat, especially due to emerging escape mutants. Even with the number of vaccinations increasing, in the United States there are around 150,000 new infections being detected each day and the death toll has now passed 675,000. Many countries are far behind the United States and have extremely low levels of vaccination, increasing the risk of new escape mutants emerging.

New and effective treatments against COVID-19 are therefore required, and one potential treatment has been found in an unlikely source by researchers at the Rosalind Franklin Institute.

The researchers have demonstrated neutralizing single domain antibodies (nanobodies) have great potential as a treatment for COVID-19 and have been shown to be effective at targeting the SARS-CoV-2 virus.

The researchers identified a unique antibody produced by llamas which is both small and stable and, in contrast to the antibody treatments currently being provided in hospitals, the llama antibody could be delivered as a nasal spray rather than intravenously. The researchers showed it is possible to produce short chains of the molecules in large and that the nanobodies bind tightly to the SARS-CoV-2 virus and neutralize it in cell culture. They were also effective as a treatment in a Syrian hamster model of COVID-19 and also effective prophylactically.

Current antibody therapies require antibodies to the SARS-CoV-2 virus to be harvested from blood samples taken from patients who have recovered from COVID-19, but nanobodies could be a much more cost-effective solution. They are far cheaper to produce, and the small size means they can easily be delivered via a nebulizer or nasal spray, which delivers the nanobodies directly to the site of infection. Also, the treatment would not need to be provided intravenously in hospitals. Patients could be prescribed the treatment for use at home.

Image Source: Rosalind Franklin Institute

To produce the nanobodies, the researchers injected part of the SARS-CoV-2 spike protein into a llama at the antibody production facility at the University of Reading. Researchers were able to purify four nanobodies (C5, H3, C1, F2) which were shown to have pmolar affinity for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The C5 and H3 nanobodies overlap the ACE2 epitope, while C1 and F2 bind to a different epitope.

The researchers showed the C1, H3, and C5 nanobodies were effective at neutralizing the Alpha and Victoria strains of SARS-CoV-2, while C1 also was also effective against the Beta strain.

When the C1 nanobody was used in a Syrian hamster model COVID-19, symptoms improved. The hamsters lost far less weight after 7 days than the control group and treated hamsters also had a lower viral load in the lungs and airways after 7 days.

“Because we can see every atom of the nanobody bound to the spike, we understand what makes these agents so special,” said James Naismith, PhD, director of the Rosalind Franklin Institute. The nanobody technology developed by the researchers could also be potentially adapted for use in treating other viral diseases.

You can read more about the research in the paper – A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19 – which was recently published in Nature Communications. DOI: 10.1038/s41467-021-25480-z