Llamas and alpacas have unique immune systems. The idea of harnessing their single-chain antibodies to control COVID-19 has been around since the start of the pandemic, and its credibility is growing. New research demonstrates that hamsters given llama antibodies suffer fewer effects when infected with SARS-CoV-2 than their untreated counterparts, and pre-dosing can stop them from getting sick altogether.
Human antibodies, like those of other mammals, are made up of double chains of proteins. Llamas and alpacas have these too, but also produce antibodies, known as nanobodies, that contain just a single protein chain. Nanobodies are widely used for diagnosis since they do a better job of distinguishing between some viruses than double-chain antibodies.
Even before the pandemic, scientists had demonstrated nanobodies from llamas injected with coronavirus spike proteins produced virus-neutralizing nanobodies. In July 2020, researchers at the Rosalind Franklin Institute showed llama nanobodies can stop SARS-CoV2's spread in cell cultures. Now, the same team report in Nature Communications they have replicated their achievement in living animals.
"While vaccines have proven extraordinarily successful, not everyone responds to vaccination and immunity can wane in individuals at different times," said the Institute's Professor James Naismith in a statement. "Having medications that can treat the virus is still going to be very important, particularly as not all of the world is being vaccinated at the same speed and there remains a risk of new variants capable of bypassing vaccine immunity emerging."
Researchers injected part of the SARS-CoV-2 spike protein into a llama named Fifi and purified four types of antibodies she produced. They then combined these into chains and got E.coli to mass-produce them, so they didn't require a large supply of llamas.
The work was being done before the Delta variant had become the dominant COVID-19 strain, but the team showed three of Fifi's nanobodies neutralized the original strain of the disease, plus the Alpha variant. One of these was also effective against the Beta variant in culture. Electron microscopy showed two of the nanobodies bind to different parts of the virus from the other two, making it harder for resistance to evolve.
Many things stop viruses (or cancers) in cultures, but fail in living organisms. However, when the team gave COVID-19 infected hamsters the nanobody chains, the hamsters lost less weight and had lower viral load in their lungs. Administration of one of the nanobodies prior to virus exposure also prevented the hamsters from getting infected.
Llama nanobodies and their artificial versions have several advantages as treatments compared to monoclonal antibodies from recovered patients. They don't need cold storage, making transportation easier – but perhaps more importantly, they can be administered through a nasal spray. This not only saves on the need to involve a trained professional, but it may also prove more acceptable to people uncomfortable with injections.
Administration straight to the respiratory system may also make the nanobodies more effective at blocking transmission than vaccines.
The team responsible are seeking funding to begin clinical trials. They are also hoping to adapt the technology so it could be rolled out much more quickly to fight future outbreaks of new respiratory diseases, rather than taking years as in this case.
