Can the blood of a llama named 'Winter' be used to protect against coronavirus?

What may be the latest hope in the hunt to develop a treatment for COVID-19 comes from an unusual source – a furry, four-year-old llama named “Winter” living on a farm in the Belgian countryside.

Researchers from the U.S. and Belgium selected the llama four years ago to be their test subject for a series of virus studies involving SARS and MERS. Their goal was to isolate the llama’s tiny, disease-fighting antibodies to use as a possible treatment for these coronaviruses.

Winter isn’t an anomaly with super-powered antibodies or anything. It just happened to be chosen out of the 130 other llamas and alpacas living on the farm for this particular research project by a team from the University of Texas at Austin, the National Institutes of Health, and Ghent University in Belgium.

Llamas have long been used in antibody research, including HIV and influenza studies, thanks to their ability to produce two types of antibodies – one that is similar to humans and one that is approximately a quarter of that size.

Those smaller antibodies, also known as single-domain antibodies or nanobodies, are able to penetrate hard-to-reach areas on spike proteins, which allow viruses, like the novel coronavirus, to enter human cells and infect them.

The llama’s nanobodies, which are created by other camelids, such as alpacas, as well as sharks, have been shown to block virus proteins more effectively than humans’ larger antibodies.

Because of this, the scientists from the U.S. and Belgium injected Winter in 2016 with spike proteins from the viruses that caused the SARS epidemic in 2003 as well as the virus that later caused the MERS outbreak in 2012.

They found that the antibodies the then nine-month-old llama created over a six-week period in response to the viruses were effective at blocking them from entering and infecting cells.

As they were writing up the results of their research, the novel coronavirus outbreak occurred and the researchers wanted to see if the antibody they developed from those viruses might be effective against the new coronavirus (SARS-CoV-2), a viral cousin of those earlier viruses.

“That was exciting to me because I’d been working on this for years,” Daniel Wrapp, a graduate student at UT Austin and co-first author of the paper, said in a press release. “But there wasn’t a big need for a coronavirus treatment then. This was just basic research. Now, this can potentially have some translational implications, too.”

According to their recent preliminary study, published in the journal Cell on Tuesday, the team of scientists were able to engineer a new antibody by linking two copies of a special kind of antibody produced by llamas. This new antibody is able to tightly bind to the spike protein on the surface of the new coronavirus to block it from infecting cells in culture.  

“This is one of the first antibodies known to neutralize SARS-CoV-2,” Jason McLellan, an associate professor of molecular biosciences at UT Austin and co-senior author, said in a press release.

The next step, according to the team, will be to conduct preclinical studies in animals, such as hamsters or non-human primates, before eventually testing the antibody in humans.

While the research is still in its early stages, the scientists said they hope to develop a treatment, not a vaccine, using the antibody, which would provide immediate protection against the new coronavirus.

“Vaccines have to be given a month or two before infection to provide protection,” McLellan said. “With antibody therapies, you’re directly giving somebody the protective antibodies and so, immediately after treatment, they should be protected. The antibodies could also be used to treat somebody who is already sick to lessen the severity of the disease.”

‘JURY’S STILL OUT’

While the scientists expressed hope that their newly engineered antibody from the llama could be used to prevent and treat novel coronavirus in the future, an Ontario virologist said there are a few caveats to this study that should be taken into account.

Brian Lichty, a virologist at McMaster University in Hamilton, Ont., said the study’s authors, and many other researchers, have been targeting one particular cell receptor, known as ACE2, that appears to allow the new coronavirus to enter and infect human cells, with their antibodies.

However, Lichty said there is good evidence to suggest there are other receptors besides ACE2 that SARS-CoV-2 can use to enter cells and infect them.

“They only show blocking of one point of entry,” he told CTVNews.ca during a telephone interview on Friday. “It doesn't demonstrate that it won’t get in by these other receptors.”

Lichty also said it’s difficult to know how effective the llama’s antibodies will be against the actual SARS-CoV-2 virus because they tested them with an artificial pseudo-typed virus called Vesicular stomatitis virus (VSV), which has been used extensively in virus studies.

“It’s a great tool, but it’s a very different virus,” he said. “That’s not a coronavirus that they’re blocking. It should work on the actual SARS-CoV-2, but they didn’t demonstrate that.”

The virologist said he suspects it will take a “cocktail” of different antibodies that would be able to bind on to several different places on the spike protein to prevent it from entering human cells.

“You would use the cocktail so that if one of those spikes changes [or mutates], you’ve got another antibody or protein that will bind to one of the other spots,” he explained.

Lichty said he doesn’t want people to get their hopes up about studies like the llama one because “until people start putting these [antibodies] into humans, the jury’s still out.” 

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