The Seattle area, which was hit with the country’s first outbreak of the novel coronavirus, is also fast becoming a hub for studies of COVID-19 vaccines.

The world’s first vaccine clinical trial was launched here on March 16. Now, three additional late-stage trials are about to begin, with the goal of enrolling 1,700 volunteers across the Puget Sound region willing to roll up their sleeves for experimental injections.

“A vaccine is something our country needs and the world needs,” said Dr. Julie McElrath of the Fred Hutchinson Cancer Research Center, who’s leading one of the trials. “Hopefully, people will want to be part of that effort and we can learn together.”

The vaccines to be evaluated locally include several of the leading candidates backed by the federal Operation Warp Speed initiative. Having so many major experiments underway simultaneously is highly unusual, but reflects the urgency created by a pandemic that has already killed more than 235,000 Americans and 1.2 million people worldwide, McElrath said.

The new trials are coinciding with a massive surge in infections. From France to Italy and Greece, several European nations have reimposed partial lockdowns. New infections in the U.S. spiked above 100,000 a day for the first time last week, while Washington state also set a record with nearly 1,500 cases on Nov. 3. In some parts of the country, hospitalizations are doubling every two to three weeks.

Vaccines will be key to bringing the virus under control, and the hope is that several of those now in Phase 3 trials will prove effective, said UW Medicine virologist Dr. Anna Wald, who’s leading a trial at Harborview Medical Center. Worldwide, 50 experimental vaccines are in human trials, and nearly 90 are being tested in animals.

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“We need all kinds of vaccines,” Wald said. “We can’t just rely on one.”

The vaccines being tested in Seattle reflect a range of approaches to inducing a robust, lasting immune response against the virus. The common denominator among them is safely exposing people’s immune systems to the spike proteins that stud the surface of the virus and allow it to bind to and infect human cells.

McElrath’s group at The Hutch hopes to enroll 500 volunteers to test pharmaceutical company AstraZeneca’s two-dose vaccine. It uses an inactivated form of a chimpanzee cold virus as a vector, or transport vehicle, to slip the genetic code for the spike protein into human cells. The cells are tricked into producing the spike protein, which is harmless on its own but sufficiently foreign and alarming that the body mounts an immune response to attack it.

At Kaiser Permanente Washington Health Research Institute in Seattle, Dr. Lisa Jackson is launching a 200-person experiment with a similar vaccine from Johnson & Johnson. Instead of a chimp virus, its vector is a rare type of human cold virus, modified so it can’t cause sickness. The J&J vaccine is also the only leading candidate that seems to work with just a single shot.

“A single dose does make things much less complicated if you’re rolling it out into widespread use,” Jackson said.

The viral vector technology isn’t brand new, which is also an advantage, she said. It’s been tested in several experimental vaccines, including against Ebola and HIV, though none have been approved for human use in the U.S.

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Jackson was also a leader of the world’s inaugural COVID-19 vaccine trial in Seattle, which evaluated the safety and potential efficacy of another type of vaccine with a novel approach to triggering immunity.

Produced by the biotech company Moderna, the shots directly deliver snippets of coronavirus messenger RNA, which contains instructions for producing the spike protein. The machinery in human cells reads the instructions and cranks out copies.

No messenger RNA vaccines have yet been approved. The initial study by Jackson and her colleagues found that the vaccine was generally safe and induced a strong immune response after two shots. Phase 3 trials, which determine whether a vaccine actually works to protect people from infection and illness, are underway now at Kaiser in Seattle and dozens of other sites around the world. (The Moderna trial is not accepting new volunteers.)

The biggest of the new local trials is Wald’s at Harborview. She and her colleagues hope to sign up 1,000 volunteers to help test a vaccine produced by the Maryland company Novavax. It’s not as far along in the process as several other candidates, but it is based on a tried-and-true approach that has been used in vaccines for shingles and hepatitis B.

Novavax mass produces copies of the novel coronavirus spike protein, attaches them to microscopic particles and adds an adjuvant — a substance that revs up the immune system.

“All of the vaccines have their pluses and minuses,” Wald said. “In some ways this is a very traditional vaccine construction, and there might be some people who are more comfortable with that.”

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The Seattle-area trial sites are part of the vast network required to handle the numbers of participants. The AstraZeneca, Novavax and Moderna trials are each enrolling 30,000 people. The target for the Johnson & Johnson vaccine trial is 60,000 volunteers at 215 sites.

Many volunteers will get a placebo, and high enrollment is necessary to answer the question of whether they are more likely to get infected than people who get the vaccine — or whether the vaccine reduces the severity of illness. The trials are randomized and blinded, which means even the researchers won’t know who got placebo or vaccine.

How long it takes to get meaningful results depends, unfortunately, on how quickly people get sick. The large Novavax trial Wald is part of, for example, won’t be able to draw any conclusions about the vaccine’s effectiveness until about 100 people out of the 30,000 participants become infected. After that, the trials will continue for up to two years to track changes in volunteers’ immune responses.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in a recent online interview that it’s possible the Food and Drug Administration could approve the first vaccine sometime in January, though he warned it might be later than that.

If there’s any silver lining to the ongoing upswing in cases, it’s that the initial vaccine trial results might come more quickly, the researchers say. They also hope to enroll people at higher risk of contracting the virus — either because of their jobs, living situation or age.

Communities of color, which have been disproportionately impacted by the pandemic, are also a primary focus.

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People 65 or older, who are often excluded from clinical trials, are another key part of the COVID-19 vaccine studies, McElrath said. Most of the local trials are open to nursing home or assisted-living residents and people with underlying conditions, like heart disease and diabetes, which make them vulnerable to severe COVID-19.

While everyone wants to know when a vaccine will be widely available, it’s important not to take shortcuts that could imperil safety or compromise the results, Jackson said.

Both the AstraZenca and Johnson & Johnson trials were recently paused to investigate adverse reactions in volunteers. After reviewing the incidents, the FDA concluded it was safe to resume both trials.

“These things take time,” Jackson said. “We’re just going to have to let the process play out.”

And while the drive to develop, test and distribute COVID-19 vaccines is often described as a race, the three Seattle researchers are more collaborative than competitive.

“I feel like we are racing against the epidemic,” Wald said, “not against each other.”

For more information or to volunteer

https://www.coronaviruspreventionnetwork.org/ is a clearinghouse site where volunteers can learn about a wide range of vaccine trials and register to participate.

For the Novavax trial at Harborview, complete the volunteer screening registry at the link above and enter the site code “UWVR.”

For the AstraZeneca trial at Fred Hutch, enter the site code “SVTU.” Potential volunteers can also email info@seattlevaccines.org or call or text 206-667-2300.

For the Kaiser Permanent Washington study of the Johnson & Johnson vaccine, register at: corona.kpwashingtonresearch.org.