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UW researchers design ultrapotent COVID-19 vaccine candidate

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UW researchers design ultrapotent COVID-19 vaccine candidate

An ambulance sits outside of the UW Medical Center emergency room on April 1, 2020.

As the search for an effective COVID-19 vaccine continues, a team of researchers at UW Medicine have developed a vaccine candidate that demonstrated ultra-potency in preclinical data.

The study was a collaboration between the labs of assistant professor of biochemistry Neil King and associate professor of biochemistry David Veesler. 

The spike protein on the surface of SARS-CoV-2 mediates the entry of the virus into host cells and has been the focus of many vaccine platforms, as it is the target of antibodies produced by the immune system. 

Brooke Fiala, a research scientist in King’s lab and co-lead author of the study, said the team focused on a specific piece of the spike protein that binds to host cell receptors, known as the receptor-binding domain (RBD).

The other component of the vaccine was the self-assembling protein nanoparticle, which was developed using computational vaccine design technology invented by King. 

“Displaying the SARS-CoV-2 RBD on [the nanoparticle] elicits a more potent immune response because vertebrate immune systems — including that of humans — have evolved to detect repetition as a danger signal,” King said. “So when the immune system sees the repetitive RBD array on the nanoparticle, it attacks it with gusto.”

The study showed that the vaccine, in which 60 copies of the RBD were displayed on the nanoparticle, induced extremely high levels of neutralizing antibodies in mice and a nonhuman primate.

Although the results were exciting, King said the success of the vaccine wasn’t surprising to the team.

“We expected the vaccine to be quite potent based on other nanoparticle vaccines we have tested over the last few years,” King said. “We were happy that the vaccine looked good in the lab, as it is our job to make next-generation vaccines.”

This vaccine also has other important features of an effective COVID-19 vaccine. According to Fiala, these features include its ability to be mass-manufactured, being stable at room temperature or in the fridge for several weeks, and only requiring small doses to elicit a strong antibody response.

With this being the team’s first time navigating a pandemic as a vaccine development group, Fiala said the biggest challenge for them was the speed of production and testing, but the collaborative nature of the project made it a rewarding experience.

“Our core teams eagerly came together with hefty optimism and poured themselves into this project,” Fiala said. “It was beautiful to see the immense teamwork, and I feel grateful to have been a part of it.”

Currently, King said the vaccine is being manufactured under carefully controlled conditions by licensees including Icosavax, a Seattle biotechnology company co-founded by King in 2019, and SK Bioscience, a South Korean biopharmaceutical company. 

“This is a very complex and expensive process, but these companies have deep expertise that is allowing them to move quickly and carefully,” King said. “They are also running tests to make sure the vaccine is safe, and once they get permission from the appropriate regulatory authorities, they will evaluate the vaccine in human clinical trials.”

King said that the researchers have learned a lot so far from developing this vaccine —  particularly how putting key parts of viral glycoproteins, such as the RBD, on nanoparticles can be a good approach to making ultrapotent vaccines.

However, King said he hopes the next pandemic will look different.

“In the future, we’d prefer to prevent pandemics rather than respond to them,” King said. “So it’s critical to learn how to make vaccines that provide very broad protection against lots of different coronaviruses. This is something we’re working very hard on.”

Reach reporter Shannon Hong at news@dailyuw.com. Twitter: @shannonjhhong

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(1) comment

CptSuprstition

You can do this, guys! I know you can get there. This one's pretty promising and I'm sure it's only a matter of time before it makes the rounds.

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