An image of the nanoparticle with spike proteins used in Icosavax’s COVID-19 vaccine candidate. (Photo by Ian Haydon/UW Institute for Protein Design)

When the COVID-19 pandemic hit, University of Washington scientist Deborah Fuller did a quick pivot to the new virus. Her skills in vaccine research had been honed for many years on HIV, a tricky virus that has eluded the best attempts at vaccine design. She had the chops for the new challenge.

“COVID-19 is a piece of cake compared to HIV,” she said. The virus that causes COVID-19 changes less and has fewer hide-outs in the body, and so there was more hope it could be quelled with a vaccine. “HIV is the highest bar.”

University of Washington professor Deborah Fuller. (UW Photo)

Fuller is just one of many Seattle-area vaccine scientists that have focused their studies on COVID-19, building on the region’s deep roots in vaccine research on HIV and other tough-to-beat pathogens.

“Seattle is one of the great places that is doing vaccine research in the country,” said Larry Corey, director emeritus of Fred Hutchinson Cancer Research Center. When it comes to the pandemic, “we’ve been instrumental,” he said. The result has been a host of clinical trials, emerging vaccine designs and a few burgeoning startups.

The currently authorized vaccines are highly effective, particularly the RNA vaccines made by Pfizer and Moderna. And the Seattle region has had a major role in their development.

Dr. Larry Corey. (Fred Hutch Photo)

The Moderna vaccine, for instance, was tested in an early clinical trial at Kaiser Permanente, with Seattle tech worker Jennifer Haller first in line in the inaugural U.S. COVID-19 vaccine trial.

Corey, who for years has run the world’s largest publicly-funded network of HIV vaccine trials, was tapped by the U.S. National Institutes of Health to head the COVID-19 Prevention Network. That network coordinated massive phase 3 vaccines trials at more than 70 clinical trial sites, testing shots made by Moderna, AstraZeneca, Johnson & Johnson, and Novavax.

But despite the success of the current vaccines, researchers say there is room for new vaccines that may be easier to manufacture, have greater stability at room temperature, or are easier to engineer against emerging variants.

“When you’re faced with an enormous challenge like a virus like HIV that undergoes enormous diversity, and it’s very hard to chase down, it forces investigators to really innovate,” said Fuller. As a result, Seattle researchers “think outside the box,” she said. Innovative vaccine designs may in turn be used to build better shots against HIV or protect the world from the next pandemic.

As one Seattle-area vaccine startup, Icosavax, goes public this week, we’ve rounded up some of the vaccine research in the Seattle area, highlighting some of the factors that make this science ecosystem so vibrant: scrappy startups, stable funding support and strong research institutions.

Taking it to trial

Icosavax and another Seattle-area startup, HDT Bio, are initiating clinical trials for their COVID-19 vaccine candidates.

Icosavax, spun out of the UW’s Institute for Protein Design, is generating protein-based vaccines designed to mimic the structure of a virus. Their virus-like particles are built from a spherical nanoparticle studded with bits of viral spike proteins, a key component of the virus.

“It kind of looks like a virus but it’s even more optimal,” said Fuller. The proteins are computationally designed to elicit a strong immune response, and they are packed in tightly, with 60 per nanoparticle.

University of Washington biochemists and Icosavax co-founders David Baker and Neil King show off molecular models of proteins at UW’s Institute for Protein Design. (UW IPD Photo / Ian Haydon)

Icosavax initiated a phase 1 and 2 clinical trial of a COVID-19 vaccine candidate this June, and is also developing shots against two viruses that cause pneumonia.

Virus-like particles are used by already-approved vaccines for human papillomavirus and hepatitis B, which may ease the regulatory process for Icosavax’s vaccine candidates.

HDT Bio announced plans this July for a U.S. clinical trial for its RNA-based vaccine candidate. Once in the body, the RNA provides instructions to produce proteins that prompt an immune response. The RNA in the Moderna and Pfizer vaccines is encased in a nanoparticle, but the RNA in the HDT vaccine instead self-assembles onto the surface of a nanoparticle.

That design enables the RNA and the particle to be made separately, speeding manufacturing, said Fuller. In addition, the HDT RNA is also able to make copies of itself, a feature designed to reduce the amount of material needed in the vaccine and up its potency.

The company aims to generate a vaccine that is easy to manufacture, does not require deep freezing, and has the potential to work as a single shot, said Fuller. “That is going to theoretically enable better reach throughout the world.”

In addition, the approach could potentially enable plug and play manufacturing against new variants. RNA could potentially be generated against a variant and then paired with pre-made nanoparticles.

Fuller is a scientific advisor to HDT and also an investor in the company. She led a recent study testing the HDT vaccine candidate in macaques and mice. Fuller is also founder of Orlance, a Seattle-based startup investigating DNA-based vaccines for COVID-19 and other diseases.

“Pretty much all of my lab collaborates closely with the private sector,” said Fuller. “If you want to bring it out into the world, you’re going to have to partner up.”

Fuller’s lab is currently partnering with Icosavax and HDT to combine the two approaches. Early, unpublished data in non-human primates suggest that an RNA vaccine followed by a boost with a protein vaccine elicits a particularly strong immune response, she said. She is also collaborating with Icosavax on generating a DNA-based version of their vaccine.

The region’s strong research base has also helped nurture other startups working on diagnostics and therapeutics. These include Seattle-based Adaptive Biotechnologies, which developed an immune-cell based test for COVID-19 and San Francisco-based Vir Biotechnology, which is developing potential treatments for COVID-19 and other viruses. Corey is a co-founder of Vir, which is backed by Bill Gates and also collaborates with other Fred Hutch researchers.

More established companies are also involved in vaccine manufacturing in Washington, including Seattle-based AGC Biologics and Spokane-based Jubilant HollisterStier, which is making products for Novavax and India’s Bharat Biotech.

“Virology and immunology are two big areas of research intensiveness in the state of Washington, and particularly in the greater Puget Sound,” said Leslie Alexandre, CEO of the industry group Life Science Washington. “There’s been this entire pipeline.”

Funding powerhouse

Key to the pipeline has been the Bill & Melinda Gates Foundation. Icosavax’s clinical trials, for instance, are being launched with $10 million funding from the Foundation.

The foundation’s contribution to the Gavi, The Vaccine Alliance, totals about $5.7 billion. And it has committed more than $1.75 billion globally to the COVID-19 response, though it has been criticized for shifting views on vaccine patent protections and what some say is uneven support for COVAX, the international vaccine initiative. 

Other public health-oriented organizations in Seattle also support vaccine research. But the Gates Foundation has a unique role. Corey said it has been a “major part” of helping create the city’s strength in global health research and development.

The research engine

Fred Hutch has long been a leader in HIV vaccine research, with roots in the early days of the AIDS epidemic, as patients fell ill with Kaposi’s sarcoma and other cancers.

Kristen Cohen is just one HIV vaccine researcher at Fred Hutch who has turned to COVID-19. She partners with multiple pharmaceutical companies to examine how the immune system reacts to different COVID-19 vaccines, for instance showing that the Johnson & Johnson COVID-19 vaccine raises a robust immune response.

Cohen’s research is also informing the design of new vaccines. One study suggests that an often-ignored component of the virus, called the nucleoprotein, can prompt a particularly strong type of immune response and may be a potential target for a new vaccine. That’s an approach being investigated in a trial by a Boston-based startup Gritstone Oncology.

Fred Hutch senior staff scientist Kristen Cohen. (Fred Hutch Photo)

Newly emerging vaccine designs may provide increased versatility in responding to COVID-19, but Cohen also has her eye on the more distant future. “We will want to have platforms that are easily available to react to the next pandemic,” she said. She is also working with Johnson & Johnson to adapt their COVID-19 vaccine platform to other pathogens, such as Ebola and HIV.

Meanwhile, the COVID-19 Prevention Network continues to run trials on already-authorized vaccines, examining questions such as how long immunity lasts, how well vaccines prevent transmission of the delta variant, and how well they work in people infected with HIV, said Corey.

And while some newly emerging vaccine candidates might be easier to manufacture, factors such as distribution, funding and high rates of vaccine hesitancy also impede vaccination. Only a small percentage of people in Africa are vaccinated, notes Corey.

“How much of that is technology, how much is distribution, money, world management, and the chaotic way of distributing things?” he asks. “Great technologies can be developed, but if you can’t put them in people’s arms, you’re not doing any good.”

And until most of the world is vaccinated, the whole population is at risk. “While there are still large pockets of the world that are not vaccinated the virus will have ample opportunity to evolve and to become more transmissible and potentially even more pathogenic,” said Cohen. “We’ll never be able to out-run these variants that are emerging without vaccinating a large proportion of the world population.”

Fred Hutch has compiled stories on its COVID-19 vaccine research here. Meanwhile, the University of Washington and other Seattle-area research institutions are producing a steady stream of COVID-19 studies. It’s impossible to list them all, but some examples are below. Key to progress has been the collaborations built between regional institutions and more broadly.

  • Keith Jerome, director of the UW virology lab, has been instrumental in testing and surveillance of the virus. He’s known for his lab’s work with UW’s Helen Chu, identifying the first cases in the region, and is also involved in vaccine studies. For instance, he is measuring levels of virus in people in clinical studies led at the Hutch, where he is also a professor.
  • Researchers at the UW and Virginia Mason’s Benaroya Research Institute are investigating the efficacy of booster shots. And UW’s David Veesler and his colleagues have performed studies in macaques suggesting that already-authorized vaccines may yield a robust antibody response to variants.
  • Rhea Coler at Seattle Children’s and her colleagues were involved in the first trials of the Moderna vaccine and are currently studying several vaccines in women who are pregnant or who have recently given birth.
  • Researchers at the Allen Institute for Immunology and Fred Hutch are tracking the immune responses of people with COVID-19, emerging with richly detailed studies. Similarly, scientists at the Institute for Systems Biology recently collaborated with Swedish Medical Center and others on a study comparing the immune response in people with mild, moderate and severe infection. Understanding what a robust immune response looks like could help inform the development of new vaccines.
  • Seattle’s Infectious Disease Research Institute (IDRI) is known for its work on adjuvants, substances that boost the power of vaccines. One recent study paired an adjuvant developed by IDRI and 3M with a shot developed at Duke University. The study showed robust immune responses against a broad range of corona viruses in macaques. That’s one of the end goals of vaccine research, as such a “universal vaccine” candidate could potentially fend off the next pandemic. The adjuvant is currently being tested in early-stage clinical trials in combination with a shot against another virus. That virus, not surprisingly, is HIV.
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