Scientists are pursuing multiple tracks of research in the quest for an effective treatment to combat the COVID-19 pandemic. One pathway showing some early promise involves llamas. A new study shows that antibodies from llamas can neutralize the virus that causes COVID-19.Daniel Wrapp, the co-author of that study, is a graduate student affiliated with Dartmouth College and the University of Texas at Austin. He spoke to Mitch Wertlieb about his research. Their interview has been edited and condensed for clarity.
Mitch Wertlieb: So presumably you did not just pick any animal out of a hat. Why did your team think that llamas might have antibodies that could actually help fight the coronavirus?
Daniel Wrapp: In the early 90s it was discovered that camelids, which is a group that includes llamas, alpacas, camels and a couple other animals, produced a specialized class of antibodies which are called nanobodies. The reason they're called that is because they're about half the size of the conventional antibodies that you and I would produce. And because of that smaller size, they have enhanced stability and they're also able to wedge themselves into crevices that larger antibodies wouldn't otherwise be able to access.
So in 2016, in collaboration with our colleagues at Ghent University in Belgium, we vaccinated a 4-year-old llama, named Winter, with the coronavirus spike proteins from the viruses that caused the MERS and SARS outbreaks. From the llama we were able to isolate two really potently neutralizing antibodies, one directed against MERS, one directed against SARS. And we were in the process of writing up these results when the current pandemic broke. There were no active coronavirus outbreaks when we started this research. We were just hoping to learn more about how these proteins functioned.
Before we continue, I'm pretty sure our listeners are going to want to know if Winter the llama is okay after having this injected into its system.
Winter is totally fine! Winter is grazing peacefully on a farm in Belgium. We just injected one small portion of the virus, a noninfectious portion of the virus, to elicit these antibodies, sort of prime the llama immune system against the coronaviruses. And then once we had done that, we were able to get the sequence of the antibodies which were raised in response to vaccination. Once we had those sequences, we could produce the nanobodies in lab, so we didn't have to be continuously drawing blood from these llamas, and we were able to produce recombintantly from a cell culture system for all of our experiments.
Any idea why llamas and their relatives have these special antibodies that many organisms don't?
That would be a really interesting question for an evolutionary biologist, because these smaller antibodies also exist in sharks. But it's thought that was a two distinct evolutionary events: one in llamas and one in sharks.
How confident are you that this could lead to a possible vaccine that could actually eliminate COVID-19?
There is a slight distinction between what we're proposing or reporting here and a vaccine. A vaccine, you would administer a patient something that looks like the virus so that they can raise antibodies in response to that. And then they would be protected if they ever came into contact with the actual infectious agent.
Here we would be directly administering an antibody. So it's more of a treatment than a prophylactic vaccination. That being said, vaccines aren't always super effective in the elderly. They have trouble raising an active immune response. And so we could prophylactically administer this antibody and then they would be protected for several months.
We are actively performing pre-clinical trials, testing for protection in hamsters. If that looks good, we'll move into non-human primates. And if that looks good, we'll begin phase-one clinical testing in humans.
And about how much time are we talking about with all those steps you just mentioned?
Our best estimate for the entire time course from right now until we could have an approved therapeutic on the market is about a year.
I think several years from now we will have an effective vaccine and there will be less need for treatments like this. But at the moment, even if we did have an effective vaccine, there are so many people currently infected, that a vaccine wouldn't be useful to those people. So we would need to be able to quickly administer them a treatment so they can reduce disease burden and fight off the virus more quickly.
What's important about this research for the general public to know?
I think it's a really good case for how important basic research is. When we started, there were no active coronavirus outbreaks. All of a sudden, we were writing up these results and the current pandemic hit, and because the SARS-CoV-1 virus is so similar to the causative agent of COVID-19, this research quickly became translational. It quickly became something that could have therapeutic implications.
And if we weren't doing fundamental biology, trying to understand how these proteins worked, we never would've found that out.
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