Llama nanobodies may hold key to COVID treatment, Pitt researcher finds


Wally the llama and research by Yi Shi, assistant professor in the Department of Cell Biology at Pitt’s School of Medicine, may be the key to a novel new treatment and possible prevention of SARS-CoV-2, the virus that causes COVID-19.

Yi ShiShi and Paul Duprex, head of Pitt’s Center for Vaccine Research, discussed the breakthrough at an online news conference on Nov. 5. A paper on the research, which was published on Nov. 5 by Science magazine, describes a new method to extract tiny but extremely powerful SARS-CoV-2 antibody fragments from llamas, which could be fashioned into inhalable therapeutics with the potential to prevent and treat COVID-19.

Shi’s research was one of the projects funded by Pitt’s Clinical and Translational Science Institute earlier this year to investigate problems directly related to COVID-19.

Llamas, camels and alpacas, Shi said, produce “nanobodies” that are very close in sequence and structure to human antibodies, but smaller. The nanobodies are very stable and easy to produce at a low cost, which would make ramping up production easier than some of the other antibody treatments being researched.

Enter Wally the llama, who resides on a farm in Massachusetts, and who Shi said is “currently our best friend.” Shi said the black llama resembled his black Labrador, with whom he now shares a name.

“The idea of using llama antibodies for drug discovery isn’t really new, or novel, but they’re very difficult to find with the conventional technologies,” Shi said. His lab has been working for the past three years to develop powerful technologies to identify more nanobodies.

Shi and colleagues immunized the llama with a piece of the SARS-CoV-2 spike protein and, after about two months, the animal’s immune system produced mature nanobodies against the virus. 

Using a mass spectrometry-based technique that Shi has been perfecting for the past three years, lead author Yufei Xiang, a research assistant in Shi’s lab, identified the nanobodies in Wally’s blood that bind to SARS-CoV-2 most strongly. The three-person lab also includes Zhe Sang, a Ph.D. student in the Pitt/CMU computational biology program.

Then, with the help of Pitt’s Center for Vaccine Research, the scientists exposed their nanobodies to live SARS-CoV-2 virus and found that just a fraction of a nanogram could neutralize enough virus to spare a million cells from being infected.

Shi said the nanobody works by attaching itself to the virus and preventing it from opening up, which stops it from attaching to human receptors.

“So, that means, we can link several different flavors of the COVID-19 antibodies that we developed together like a Swiss Army knife and so if the virus mutates to escape one antibody another will be there to keep it in check,” Shi said.

The small size of the nanobodies means they could be delivered as an inhalable mist, which would go directly to the lungs where they’re most needed.

Duprex said because the Center for Vaccine Research was one of the first places in the country to receive samples of the live virus, they’ve been able to “grow it in our bio-containment laboratory. And we developed tests to work out how to measure how well vaccines and other therapeutics, like these nanobodies, work.”

“What’s really nice about the Center for Vaccine Research is we have great neighbors and Dr. Shi is one of those neighbors,” Duprex said. “So whenever he needed to test how well his antibodies worked … He naturally talked to us, his neighborly biologists. … We see each other, and we chat about science often and that’s how science works by communicating and talking about new ideas.”

The virus that was used to test the nanobodies actually came from a case in Munich, Germany, which the center had obtained from one of its international collaborators.

And just in case you’re wondering, Wally is doing just fine and his job in helping find a COVID-19 treatment is done. Once the nanobodies have been identified and extracted, they can be re-created in a lab.

Susan Jones is editor of the University Times. Reach her at suejones@pitt.edu or 724-244-4042.


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