Imagine what a pandemic response might look like in an ideal world. What do you envision?

Less isolation from family and friends. Uninterrupted education for our children. Lifesaving vaccines quickly made available to everyone around the globe.

A vision so different from what we are experiencing during the COVID-19 pandemic.

We can make it happen. But we need universal vaccines that can protect us from entire families of viruses. And we need faster vaccine development when the next novel virus emerges.

Researchers at the UW Medicine Institute for Protein Design (IPD) have made impressive breakthroughs using computer-designed synthetic proteins to develop innovative vaccines. Their work is bringing us closer to a better, safer future for everyone — but philanthropic support is critical to maintaining the momentum, so we can stop the next pandemic before it starts.

Long before COVID-19, the influenza virus caused deadly global pandemics that killed tens of millions of people worldwide. Currently, our best defense is a seasonal flu vaccine, updated each year to protect against the three or four flu viruses that researchers believe are most likely to spread during the upcoming flu season.

But what if there was a universal flu vaccine that protected us against every type of flu virus?

“We really want to get to the point where we’re preventing the next pandemic, not responding to it. And the only way to do that is through broadly protective vaccines,” says Neil King, PhD, a biochemist at the IPD.

In 2019, an IPD group led by King, an assistant professor of biochemistry at the University of Washington School of Medicine, began developing a new vaccine to fight multiple flu viruses within the same family. By showing the immune system that different flu viruses share some of the same features, they hoped to teach the immune system to recognize and attack all viruses with this common weakness.

To create their vaccine, Dan Ellis, PhD ’21, a research scientist at the IPD, in collaboration with the National Institutes of Health, attached proteins in a repeating “mosaic” pattern on a custom-designed synthetic nanoparticle — a tiny protein particle that triggers an immune system response.

Why is the mosaic approach better? Current mRNA (messenger RNA) COVID-19 vaccines, such as Pfizer’s and Moderna’s, instruct your cells to build a harmless piece of the virus called the spike protein. Your immune system then learns to recognize that spike protein — the part that lets the virus enter and infect your cells — and attack it. But on its own, this spike protein doesn’t look like a natural virus, so it can be hard for your immune system to recognize.

By contrast, a nanoparticle vaccine can be designed with dozens of distinct proteins waving at your immune system like a series of unmistakable little flags. It’s a much more effective way to grab the immune system’s attention, so less vaccine is needed for a strong response.

Currently, Flu-Mos-v1, the IPD’s universal flu vaccine candidate, is in Phase 1 clinical trials; so far in animal testing, it has yielded a stronger immune response than seasonal vaccines. And, unlike seasonal vaccines, it’s even providing strong protection against flu viruses that weren’t part of the vaccine formula.

Ellis and his colleagues envision taking their nanoparticle approach even further in the future, using protein design to build vaccine prototypes for virus families with the greatest pandemic potential. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, recently proposed a new federal government program to develop vaccine prototypes for 20 virus families, which could start as early as 2022.

But the IPD’s flu vaccine efforts have already helped to create another new vaccine. When COVID-19 emerged in early 2020, the King lab — along with a network of collaborators — was ready to bring their nanoparticle approach to fight the coronavirus.

Neil King, PhD

Dan Ellis, PhD ’21

Lesi Walls, PhD ’19

When Lexi Walls, PhD ’19, a research scientist in the Department of Biochemistry at the University of Washington School of Medicine, began studying coronavirus spikes in 2015, not much was known about them. If scientists didn’t understand the spike’s structure, Walls realized, it would be difficult to treat or develop vaccines for that family of viruses.

As Walls completed her doctorate in December 2019, the SARS-CoV-2 virus (which causes COVID-19) was just emerging in Wuhan, China. Soon, COVID-19 was spreading rapidly around the world, and Walls’ research on the coronavirus’s spike protein would become an important part of the global response.

When the genetic sequences for the novel coronavirus were released in January 2020, Walls and her advisor, David Veesler, PhD, an associate professor of biochemistry at the University of Washington School of Medicine, immediately reached out to King to propose a collaboration.

“Neil jumped on board right away, and he got a huge team of people at the IPD to join forces quickly,” says Walls. “We were constantly talking, sharing data and helping each other solve problems. I had never had a collaboration like that before, and it was really fun to be working towards the same goal with the same intensity at the same time.”

The collaborators adapted the King group’s nanoparticle design to create a new COVID-19 vaccine candidate, named RBD-I53-50. Unlike mRNA vaccines, RBD-I53-50 is shelf-stable, so it’s easier to store and doesn’t need refrigeration, an important factor for global distribution. RBD-I53-50 focuses on the Achilles’ heel of the SARS-CoV-2 spike protein, called the receptor-binding domain, driving the immune system to block entry of the virus into our cells.

With funding from the Bill & Melinda Gates Foundation and the Coalition for Epidemic Preparedness Innovations (CEPI), the Veesler and King labs teamed up with the IPD spinout company Icosavax and SK bioscience, based in South Korea, to develop the vaccine. In late 2020, SK bioscience began a combined Phase 1/2 clinical study, which is currently in the second stage. And in August 2021, they received support for a Phase 3 study, bringing the vaccine another step closer to approval and distribution.

Although the RBD-I53-50 vaccine is advancing quickly, Ellis emphasizes that years of scientific research laid the foundation for its development.

“The trajectory of vaccine research isn’t always straight,” says Ellis. “But even if research doesn’t lead to a successful vaccine for one virus, it can enable very important developments for other viruses. For example, even though we don’t yet have a successful HIV vaccine, that research has made many other vaccines possible, including for COVID-19. So preparing for as many pandemic threats as possible will advance science and the future of vaccines.”

And the IPD’s long-term vision is even more ambitious. They want to significantly expand the computing power of their protein-design software so new vaccine candidates like RBD-I53-50 can be developed and made ready for testing in just weeks.

Today, we’re still facing COVID-19. But it’s only a matter of time until the next viral threat emerges. So how can we get closer to a pandemic-free tomorrow?

Throughout the pandemic, philanthropic support has been critical in empowering the IPD’s rapid response. Their groundbreaking work on nanoparticle vaccines was supported by the Bill & Melinda Gates Foundation, the National Institutes of Health, and gifts from Open Philanthropy, The Audacious Project, Jodi Green and Mike Halperin, Nicolas and Leslie Hanauer, anonymous donors and other granting agencies.

“The role of philanthropy in catalyzing the protein design revolution can’t be overstated,” says King. “It’s been absolutely essential, allowing us to seize the moment by providing flexible funding that we can direct to the most important problems of the day. When SARS-CoV-2 hit, philanthropic support enabled us to immediately pivot and attack this problem with everything we had.”

Soon, the IPD’s work will receive additional funding. David Baker, PhD, director of the IPD, is the 2021 recipient of the Breakthrough Prize in Life Sciences, which recognizes the world’s top scientists working in the fundamental sciences. This prestigious award includes a $3 million prize, the full amount of which Baker is donating to the IPD. Baker’s gift — which was matched generously by friends of the IPD — establishes the Breakthrough Fund at Seattle Foundation, which solely supports the IPD to advance the rapidly developing field of protein design.

But ongoing support will be needed to keep advancing the IPD’s bold mission.

Now, let’s imagine a brighter future. Universal vaccines could protect us from all strains of flu or SARS-CoV-2. The next time a new viral threat begins to spread, we could have vaccine prototypes already stockpiled, allowing us to develop vaccine candidates in a matter of weeks. No one would ever have to endure a global pandemic like COVID-19 again. And, with the help of philanthropic support, protein design can make it all possible.

Written by Stephanie Perry

DIVE DEEPER INTO PROTEIN DESIGN

Watch a TED Talk featuring David Baker on how the IPD creates new proteins.

Learn about the IPD response to 21st-century challenges.
Meet the UW researchers creating COVID-19 vaccines and treatments.

See how protein design is helping to create “third-generation” COVID-19 RNA vaccines.

HELP STOP THE NEXT PANDEMIC BEFORE IT STARTS

If you’d like to help the Institute for Protein Design prevent the next pandemic, make a gift to the IPD Director’s Fund today.

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