Covid 19: antibodies and llamas

While we wait for a vaccine for Covid 19, it's possible that members of the camel family could be coming to our rescue with a treatment. Scientists in America have isolated a class of antibodies from a llama vaccinated with a coronavirus. These antibodies are called nanobodies - they're like a miniature version of one of our human antibodies, and they work the same way, but they may even - on account of their small size - be able to access and neutralise parts of the virus that chunkier antibodies can't get to. Daniel Wrapp is at the University of Texas at Austin…

Daniel - We started this work in 2016 when there was no active coronavirus outbreak. And we were trying to understand the mechanisms that allowed the coronaviruses to enter into host cells and infect us. To do that, we vaccinated a llama named Winter with proteins from coronaviruses that had emerged into the human population previously.

Chris - Now, what were you hoping to learn by doing this? And why did you pick on Winter the llama?

Daniel - When we started, there were no, uh, approved vaccines or therapeutics for any coronaviruses. And in fact, that's still the case. So we were hoping that we were able to elicit antibodies from this llama, that bound to portions of the coronavirus that are critical for its function and prevent it from entering into host cells. And the reason why we picked a llama is because llamas are known to produce a specialised class of antibodies that humans aren't capable of producing. Those antibodies are about half the size of the antibodies that you and I would produce. And because of that smaller size, they're able to bind to small crevices and pockets that otherwise wouldn't be accessible to larger antibodies.

Chris - Why do llamas do this then?

Daniel - Good question. We think it's sort of just an evolutionary quirk that arose, and because it was beneficial for the llamas to be able to fight off infections, it stuck around. Sharks do a similar thing, but we think they're probably two distinct evolutionary events that just spontaneously arose.

Chris - And what about animals that look a bit like llamas? Because alpacas look like mini llamas. Do they do that as well?

Daniel - They do, yes. It's a, it's a group called camelids which includes llamas, camels, alpacas, and a couple other organisms.

Chris - And your idea then was we make them make these mini antibodies that might be endowed with the ability to reach parts of the virus that other antibodies might not. A bit like the sort of antibody equivalent of Heineken beer and what, then you could use those therapeutically, or use them to understand the virus better? What was your motivation?

Daniel - Yeah, we were trying to sort of use them to understand the virus better and if they were capable of neutralising the virus, then there would be potential therapeutic candidates. We found one mini antibody, or it's sometimes called the nanobody, that was capable of very potently, neutralising a virus that caused a Middle Eastern respiratory syndrome outbreak in 2012. And one that was capable of neutralising the virus that caused severe acute respiratory syndrome coronavirus in 2002.

Chris - How do you go then from one of these nanobodies, mini antibodies in a llama, to something that will help a patient who's infected with coronavirus of the COVID-19 type today?

Daniel - Fortunately, the antibodies that we isolated from the llama were actually so potent that we didn't have to change them much at all. Theoretically, we could take those antibodies, administer them directly to a patient, and they would be able to fight off COVID-19 more easily with the help of that treatment.

Chris - Where would you get the antibodies from though? Would you have to basically turn Winter the llama into a blood donor?

Daniel - Using this llama that we vaccinated, we identified the gene that encodes for the exact antibody that we're interested in. And now that we have that genetic information, we can put it into cells in a dish growing in the laboratory, and we can scale that up for bulk production.

Chris - And have you actually tried this against the new coronavirus? Because you've tested it against the original SARS, you've tested it against this Middle Eastern respiratory syndrome virus, have you actually challenged an individual or an animal with the new coronavirus and then shown that these mini antibodies work?

Daniel - So we haven't tested this in an animal yet, but we have done it using just cells in a dish in the laboratory. Uh, and we did see protection against the COVID-19 coronavirus. So we're optimistic that when we move into hamsters, which is going to be our first test organism, that we'll see the same effect.

Chris - And do you know how it's working?

Daniel - Yes. So the way that it works is it binds to the portion of the coronavirus that attaches to our host cells. So basically the antibody is preventing that attachment from taking place and therefore the virus can't infect.

Chris - Now, given that the llama can make antibodies, is that not just easier, since we're going to have to put these antibodies into people to treat them, is it not just easier to do to people what you did to the llama and make people make normal human antibodies?

Daniel - Yeah, the vaccination would be ideal, but as sort of a stop gap until we have an approved vaccine, this will be useful for people who have already come into contact with the virus, because you have to be administered a vaccine probably about two months before you would ever come into contact with coronavirus. So a vaccine won't be useful for people who are already infected, And there's also some interest in administering it prophylactically to the elderly, who aren't always able to raise an effective immune response upon vaccination.

Chris - And you think you could make enough of these.

Daniel - Yeah, we've scaled up production and we get very good yields. So we're optimistic about being able to produce sufficient quantities.