A COVID-19 treatment inspired by llamas

When llamas encounter pathogens like viruses and bacteria, their immune systems fight them off with two weapons: antibodies much like those made by the human body and much smaller antibodies called single-domain antibodies or “nanobodies.” Now, those nanobodies have inspired a potential treatment for COVID-19 that may be able to be delivered straight to the lungs, where the virus tends to set up shop.

Scientists from the University of Texas (UT) at Austin, the National Institutes of Health and Ghent University in Belgium developed a treatment that links two nanobodies isolated from a llama to create an antibody that binds to the spike protein on the coronavirus that causes COVID-19. That bond prevented the virus from invading cells, the researchers reported (PDF) in the journal Cell.

The researchers actually started working on the treatment in 2016, when they were studying two related coronaviruses, SARS-CoV-1 and MERS-CoV. They injected a llama named Winter with spike proteins from the viruses. Six weeks later, they collected her blood and isolated antibodies that had bound to the protein.

After SARS-CoV-2 emerged, sparking the COVID-19 pandemic, the scientists built on their earlier experiment, linking two copies of the llama nanobody that had worked against SARS-CoV-1. Now that they’ve shown the engineered antibody can neutralize the new virus in cell cultures, they’re planning preclinical studies in rodents and nonhuman primates.

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Llamas and other members of the camelid family have long been of interest to medical researchers because of the single-domain antibodies they produce. In 2018, for example, a scientific team including Scripps Research Institute and Janssen scientists described an experimental flu vaccine they developed by immunizing llamas against the flu and then isolating broadly neutralizing single-domain antibodies (sdAbs) from them. Because the sdAbs target a region of the virus that doesn’t mutate, the researchers believe a llama-inspired vaccine could offer more universal protection than standard seasonal flu vaccines do.

Camelids have also inspired experimental treatments for cancer and multiple sclerosis that capitalize on the tendency of the antibodies to bind more tightly to therapeutic targets than human-inspired antibodies can.

Another advantage of llama nanobodies is their size, said Daniel Wrapp, a graduate student at UT Austin and co-author of the new paper. They’re about a quarter of the size of human antibodies—small enough to be nebulized and delivered straight to the lungs via an inhaler.

"That makes them potentially really interesting as a drug for a respiratory pathogen because you're delivering it right to the site of infection," Wrapp said in a statement.