By Chiung-Wei Huang
At sunrise, when the North Carolina sky slowly wakes up to light blue, Kevin Saunders gets into his white coat and is ready to dive into his research.
As a director of research at the Duke Human Vaccine Institute, Saunders studies the human immunodeficiency virus (HIV) with hopes of discovering a vaccine that could prevent transmission of the virus and the disease that goes along with it.
Then COVID-19 came along, and his vaccine research took a sharp detour.
“Since the pandemic, we started to work more on coronavirus,” Saunders said in an interview at the end of June. “We had to learn about it and to build all of the vaccine tools.”
Funding for COVID-19 research was available quickly in the early days of the pandemic. Researchers who wanted to tackle this global public threat not only shifted their research focus, they also were drawn to the funding possibilities.
Before the pandemic, securing research funding could be difficult, and often slow. It can take as many as six months, sometimes longer, for the money to come in. That’s a time frame that happens only if everything goes well, according to Saunders.
To get the ball rolling, they need to write a grant proposal. Once it’s approved for funding, they need to get the right people and experts. They also need to check the equipment to make sure it can be used to test the new ideas.
Without funding lined up quickly, it can be nearly impossible to shift the focus of an entrenched lab. Almost like changing the direction of a big ship, a push is needed.
The grant money gave Saunders and his team that push.
Federal agencies and state governments also pushed the money out quickly for coronavirus research.
“They did a great job getting set up to give money out,” Holden Thorp, editor-in-chief of the American Association for the Advancement of Science’s Science Journals, said in a phone interview in July.
Thorp is also a former UNC-Chapel Hill chancellor and scientist with many ties to North Carolina.
“There were labs that had money to pivot quickly. So I think everybody did an excellent job of dropping what they were doing to work on this,” he added.
Turning the ship around
The Duke Human Vaccine Institute, established in 1990, is a place where researchers work to develop vaccines and drugs. With about 200 staff members and scientists, the diseases they have tackled include HIV, flu, SARS, Ebola, and most recently, SARS coronavirus 2 (SARS-CoV-2).
In March 2020, Gov. Roy Cooper issued an executive order that banned gatherings of more than 10 people, leaving many research activities suspended while labs tried to figure out how to continue important work and adhere to social distancing recommendations.
Saunders and the Duke team didn’t slow down, though. Within a month of working from home, he and his co-workers came up with ideas for developing a COVID vaccine.
“The techniques we do for HIV are the same techniques that we use for SARS coronavirus. So once you learn the techniques, you can change out which virus at any time,” Saunders said.
The vaccine construction and equipment was not a big issue, but the funding was. If he went with the new grant application process, he might not be able to pivot into coronavirus quickly.
However, two long-running programs at Saunders’ lab laid the groundwork for the quick response.
The National Institutes of Health (NIH), a federal agency that supports health-related research at more than 2,500 universities and other organizations across the country, has provided continuous funding to Saunders’ group.
Saunders turned to the NIH to get the necessary approval to refocus the lab’s vaccine efforts toward coronavirus vaccines. The NIH approved a grant for repurposing the research.
“That’s really what allowed us to get started,” Saunders said. “We had the resources, we had the expertise to be able to do it, and we were able to find a little bit of money at first.”
Another federal agency, the U.S. Defense Advanced Research Project Agency (DARPA), has funded the Duke Human Vaccine Institute since 2017. One of the goals of DARPA’s Pandemic Prevention Platform (DARPA P3) is to find or develop antibodies that could respond to any new virus that might quickly cause a pandemic.
That “seemed to fit really well with SARS-CoV-2,” Saunders said.
With money seeded, Saunders assembled a research team to start to evaluate antibodies that could target the SARS-CoV-2 virus. For a few months starting in April 2020, the researcher and his team spent all their time on COVID studies.
Finding antibodies capable of blocking the new virus, SARS-CoV-2, had become a global priority.
With the lab analysts, staff scientists and technicians, Saunders and his colleagues examined antibodies isolated from infected individuals, hoping to identify a potent one that could block the transmission of coronaviruses.
During one July week, Saunders said, he and his team examined nearly 1,000 antibodies, an ambitious undertaking that required many people on deck at all hours and a good bit of time.
“People came in at 6 a.m. Some people came in at midnight. They worked on Saturdays and Sundays,” he said. “There’s an amazing amount of dedication.”
Keep it moving
The state of North Carolina also provided funds that enabled Saunders and others at the Vaccine Institute to quickly shift the rest of the vaccine studies.
The state funding, different from NIH and DARPA P3, allowed Saunders’ team to focus on coronavirus antibodies and vaccine studies.
In that case, the funding showed up much quicker. Rather than have to wait for several months for federal funds, Saunders and his team did not have to take a break from their COVID research.
“That’s how we were able to have any effect on the pandemic moving forward,” he said. “Whatever ideas we could come up with and how quickly we could make them become our job, as opposed to trying to figure out how to pay for it.”
What the state grant allowed the researchers to do was test antibodies on lab animals, Saunders said.
Some of the antibodies they examined had neutralizing powers against SARS-CoV-2. At least one showed great promise, according to Saunders.
SARS-CoV, which caused the SARS outbreak in 2003 and 774 deaths, as well as two other SARS-related bat viruses, also showed vulnerability to the antibody.
“When we found this antibody, we thought we would be able to contribute protection against the next outbreak,” Saunders said.
Making a vaccine that would not only work against SARS-CoV-2 but could work against multiple coronaviruses, was something that Saunders and his colleagues were thinking about as they dove into their research.
“If we can make a vaccine generate the same type of antibody, then we would have protection against multiple viruses,” Saunders said.
Saunders collaborated with researchers at Duke and other institutions to make mRNA molecules. Similar to the Pfizer and Moderna vaccines used today, the mRNA can guide body cells to produce the particular antibody.
They tested their vaccines on animals to evaluate the level of antibodies produced.
They published their results in Nature Journal this May.
“There have been three coronavirus epidemics in the past 20 years, so there is a need to develop effective vaccines that can target these pathogens prior to the next pandemic,” Barton Haynes, director of the Duke Human Vaccine Institute, said in a statement the day the report was published.
“This work represents a platform that could prevent, rapidly temper, or extinguish a pandemic,” he added.
The study was performed in non-human tests, according to the report.
“We’re working to get this particular vaccine candidate made … so it can be put into humans in what’s called a Phase 1 safety trial and get it through that trial as quickly as possible,” Haynes said in a briefing later in May.
Anchored to the making
There will be a mix of researchers who either stay with COVID studies or return to their original research, Thorp said during the July phone interview.
The good news, Thorp added, is that the pandemic highlighted the need for funding to do important scientific research.
“NIH will and [the National Science Foundation] will continue to have more resources because of the emphasis of the Biden administration on science,” Thorp said.
“I think it’s clear that there is more money for science,” he added
Saunders and his colleagues have shifted back to more HIV research, devoting nearly 80 percent of their time to their long-running projects. Developing the HIV vaccine is “always going to be part of my lab,” Saunders said in the interview.
The pandemic, and the quick funding shift toward COVID research, has helped to bring a new interest and understanding among many about the importance of science and health research projects.
“The spotlight is on vaccine development right now,” Saunders said in the May briefing. “People who were not necessarily focused on what we did before this pandemic are paying attention to it.”
In the interview, he added that “we want to have the best training and understand the concept that they can apply to whatever virus.”