University of Washington researchers are looking to sharks for a new COVID-19 treatment | Free

“Sharks have a very unique immune system and antibody structure,” said Aaron LeBeau, a professor of pathology and laboratory medicine who helped lead the study. “They can basically do what a giant human antibody can do with a large protein, with a very small protein.”

LeBeau and his lab at UW School of Medicine and Public Health have worked with researchers at the University of Minnesota and the Scottish biotechnology company Elasmogen to develop these shark antibodies for therapeutic use. Although not readily available for human treatment, developing this technology may help in future outbreaks.

“In the future, shark antibodies could be used for other coronavirus outbreaks and coronavirus variants,” Rubeau said.

“Weird little antibody”

Caroline Barelle, CEO of Elasmogen, said the technology was first developed at the University of Aberdeen in Scotland, where she and other scientists use specialized antibodies to have the most adaptive immune system similar to humans. I was studying ancient vertebrates.

After launching Elasmogen in 2016, Barelle and her team built a library with hundreds of thousands of artificial shark antibodies. This is the first of its kind. Across the ocean, Lebeau was just in the shark’s antibody after conducting a cancer study in a llama with a similar immune system.

“It was this discovery that sharks, or Elasmobranchia (the origin of the name Elasmobranchia), carry this kind of quirky little antibody that is part of the adaptive immune system,” Barrel said.

Part of the reason that makes shark antibodies so unique is their size. According to Barrel, these are one-tenth the size of human antibodies, so they are very effective at wedged into every corner of the diseased molecule.

“They bind better and are more involved in their targets than most human antibodies,” Le Beau said. “We want to say you get more value for your money. They are small, but they are good.”

Shark antibodies are so accurate that they can neutralize the virus without damaging the host cells. And they are accustomed to surviving in the harsh environment of urea-rich shark blood.

“Shark antibodies are hardly destroyed. You can bring them to a boil and they still work,” Rubeau said.

This means that treatment with shark antibodies may be easier to store and distribute. Current COVID-19 vaccines and treatments must be kept very cold, which makes it difficult to reach all parts of the world.

A few years ago, one of LeBeau’s graduate students happened to meet Barelle at a meeting in Lisbon and was amazed at her research.

And in March 2020, Barelle and Le Beau finally met at a conference in London. At that time, they both focused on the use of shark antibodies in the treatment of cancer.

“But this virus raised an ugly head and it took all the hands of the pump. This is important to everyone here now, so let’s see what we can offer with this,” Barrel said. Said.

Erasmogen received a research grant from the Scottish Government, and Barrel immediately pulled in Lebeau. She had antibody expertise and an extensive library, and he had the ability to test them. LeBeau said overnight that he had moved from cancer research to COVID-19 research.

Elasmogen screened the entire library of shark antibodies against the protein found in COVID-19.

“We mix it up and whatever binds the diseased particles is what we pull out of the library,” Barrel said. “And, of course, it was terribly interesting because some of them actually stopped the virus infection. They are what we pursued.”

Whenever I found an attached antibody, I sent it to LeBeau’s lab for testing. There, various coronavirus proteins were injected into the shark. After having the opportunity to activate their immune system, LeBeau’s team harvested their antibodies to see how they were reacting.

“The groundbreaking moment was when I said that Erasmogen had hit twice, and when I tested those hits in our lab, it worked very well,” Le Beau said. ..

They have discovered several antibodies that effectively bind to different parts of the protein. This means that the combination of them allows for highly effective treatments.

“Actually, it’s just multiple shots to reach our goal. We want to have as many opportunities as possible to block the virus,” Barelle said.

In particular, one antibody was able to neutralize a wide range of coronaviruses, including COVID-19, SARS, and even variants found only in bats, and is believed to be the origin of COVID-19. Says.

LeBeau said that this particular antibody binds to some of the protein spikes common to all coronaviruses and does not change much in the COVID-19 variation. This is a good sign for mutants like Omicron that caused mutations to peplomers to evade the Pfizer vaccine.

Researchers still agree that vaccines are the key to fighting COVID-19. According to data from the Wisconsin Department of Health, unvaccinated people die of COVID-19 12 times more than fully vaccinated people.

However, while vaccines significantly reduce the severity of symptoms, they are not 100% guaranteed against infection, as the breakthrough case shows.

Therefore, effective COVID-19 treatment remains part of the world’s response to the virus, and shark antibodies could one day become one of those treatments.

According to LeBeau, the treatment requires years of testing, including toxicity tests in rodents and non-human primates, before it is ready for clinical trials in humans.

“But by doing this now, by participating in this research project, we can develop effective treatments for potentially horizonal coronavirus pandemics,” Le Beau said. increase.

This also applies to the mRNA technology that enabled the COVID-19 vaccine.

“People said the vaccine ran through quickly, but it wasn’t. After the SARS outbreak 20 years ago, scientists said,” Well, this peplomer is a big target for the vaccine. I started thinking. So, in reality, the COVID-19 virus vaccine has been in use for almost 20 years, “says Le Beau.

“They are beautiful creatures”

People have tested shark antibody-treated water bodies in the past, but LeBeau’s lab is one of the only labs in the world to do this kind of research.

“Shark antibodies have not been investigated in oncology or infectious disease research, so everything we do is completely new. It’s very exciting for us,” he said. Told.

And he wants to expand his lab. Currently, his four nurse sharks are about one year old, so they are only one foot long. But over the next 20 years, it will grow to 7 feet long and 300 pounds.

This means that you need more space and more food.

According to LeBeau, sharks eat about 5% of their body weight three times a week. In their native Atlantic and Caribbean, they eat shellfish that suck from the ocean floor.

“These guys are like giant vacuum cleaners,” Le Beau said.

But in the lab, they use whole foods frozen salmon and octopus. According to LeBeau, shark favorites are Key West Pink Shrimp. For Thanksgiving, Lebeau treated them as lobsters. He feeds the sharks by hand, and they enthusiastically hit and beat shards of fish.

It is clear that LeBeau pays homage to sharks as well as research. His niece named the creature after the character of James Bond — Sir. Hugo Drax was his first shark, followed by Mr. Stamper and Goldfinger. The smallest one is Nick Nack.

They draw blood every 1-2 months and spend the rest of the time playing with 78 degree water. Because they are nocturnal, they generally spend the day sleeping in cozy mountains. But when they see Lebeau enter the room, they swim to the edge of the aquarium and wait for food. He wears latex gloves and playfully strokes his back like a cat.

“My favorite part is playing around my sharks,” Le Beau said. “They are beautiful creatures. Many people are scared to see sharks, and I think they are wonderful.”