AWARDEES: Kizzmekia Corbett, Barney Graham, Emmie de Wit & Vincent Munster

FEDERAL FUNDING AGENCIES: National Institutes of Health

A Spike in Momentum

“If you’d have waited until the pandemic existed, you’d have waited too long.” This is the assessment of Steven Holland, who directs intramural (in-house) research at the National Institute of Allergy and Infectious Diseases. He should know: He oversees hundreds of researchers in multiple biomedical labs, many of whom are trying to solve pressing public health problems.

“I don’t think it is news to anyone that we pay attention to what is dramatic and dire, and we don’t pay attention to what is simply annoying or trivial. Coronaviruses are split up into seasonal viruses, like the ones that cause the common cold, and those that have taken over the global consciousness—SARS, MERS, and now SARS-CoV-2,” says Holland. Prior to the emergence of the COVID-19 pandemic, only a relatively small number of researchers were working on coronaviruses. Those researchers—including 2020 Golden Goose awardees Kizzmekia Corbett, Barney Graham, Emmie de Wit and Vincent Munster—have used their expertise in SARS, MERS, and other viruses like Ebola to pivot quickly to responding to the COVID-19 pandemic.

A Noteworthy Mentor

Barney Graham has spent the past two decades at NIAID’s Vaccine Research Center in Bethesda, MD, and is currently the center’s deputy director. A turning point for him in understanding coronaviruses came in 2013 after he and his team—which included fellow 2020 Golden Goose honoree Jason McLellan—spent three years defining the structure of a protein on the respiratory syncytial virus (RSV) that is similar to the spike protein, so named for its spiky appearance, in the coronavirus causing global havoc today. Kizzmekia Corbett joined the lab the following year and jumped right into working with coronaviruses with Graham at the tail end of the MERS outbreak. While the push to develop a universal influenza vaccine was generating significant buzz and scientific enthusiasm, Corbett was drawn to coronavirus research, a relatively “quiet” field in which she felt she would have space to grow and hone her skills.

It wasn’t the first time the two had shared a lab. Corbett first met Graham as a high school intern. “He took me into his lab when I was 18 – no one would have done that,” she recalls. Since then, Graham has served as a mentor to her and others in the lab. “He’s really been one of those people who has in so many ways unselfishly given up his seat at the table [and] propelled career trajectories.”

Now they are close collaborators in the fight against COVID-19. Life has changed for Corbett, who has inspired several media profiles, though she notes “I don’t really think I’ve had time to process it.” Her work at the Vaccine Research Center is gratifying, she says, because she and her colleagues learn, problem-solve, and get better with each new virus.

Spiked Proteins

The spike protein exists on the surface of a coronavirus; it is what the virus uses to attach to and enter a cell. Originally, says Corbett, scientists “didn’t know what spike proteins looked like, because they are unstable in the lab.” Using the knowledge generated from previous work, Graham and Corbett partnered with McLellan and his team to define the structure of the SARS-CoV-2 spike protein. (For more on McLellan, read A Llama Named Winter.) None of them could have predicted just how important their ongoing basic research would become in addressing COVID-19. It gave them, in essence, a head start against the pandemic.

Thus, the NIAID team and their collaborators put their knowledge to work to develop the backbone of a COVID-19 vaccine. The vaccine candidate involves messenger RNA, or mRNA, a kind of genetic material that delivers a stabilized version of the spike protein based on the previous work with the MERS coronavirus. Explained Corbett in a NIAID video, “The messenger RNA will tell the body to present this spike protein and the body will respond by creating an immune response, and hypothetically, if all goes well, then that immune response will then be able to see a novel coronavirus before a person gets infected and prevent that infection.” An existing partnership with a pharmaceutical company, Moderna, also helped speed the process.

“It was a staggeringly short period of time” to develop a vaccine candidate, emphasizes Holland, because the work they had done on similar viruses prepared them so well for SARS-CoV-2. “It was so far out in front of anything that had been done before.” The important question though, he says, was whether the vaccine would prevent disease in humans.

A Dynamic Duo

Another NIAID duo, this one in the NIH’s Rocky Mountain Labs in Montana, have been doing their part to help answer that question and learn more about the nature of SARS-CoV-2. For Emmie de Wit, the fascination with viral outbreaks began in the early 2000s in the Netherlands, where an emergence of bird flu occurred while she was working toward her PhD at Erasmus University Rotterdam. She and her lab mates went into action to identify the virus and work on patient samples. The work became the basis for her thesis project and the foundation for a career spent investigating outbreaks.

The PhD program was fortuitous for another reason: It is where she met Vincent Munster. The pair married in 2009.

“While Emmie did a lot of work on molecular biology in her thesis, I was trying to understand where viruses come from,” Munster recalls – in particular, how they spilled from the natural world into humans. Among his projects was a stint working in the Middle East on camels during the MERS epidemic; though camels didn’t get ill with the MERS virus, they spread it quite effectively to humans. In fact, Munster used his starter funds at NIH to acquire three camels, a purchase he recalls having to then explain to new boss Dr. Anthony Fauci, NIAID’s longtime director and now a household name as a leading federal infectious disease expert. For the record, Fauci was supportive.

Munster and de Wit have separate research labs at the Rocky Mountain Labs, where they moved in 2009. “We have different skills sets, and when you put them together, they work really well,” de Wit points out. The common thread of their work involves investigating outbreaks. They work with animals to learn about viruses and create tests to figure out whether vaccine candidates and treatments have the potential to work in humans.

With SARS-CoV-2, their skills in developing animal models for previous viruses came in handy, and like their colleagues in Bethesda, they were able to quickly get their COVID-19 response research up and running. When the pair first learned of the new virus, “we immediately dropped everything,” de Wit says. Since that moment in January, using routines devised from their earlier investigations, they have developed new ways to understand the virus and test multiple vaccine candidates and potential antiviral treatments.

Promising Results

Thanks to the work of Corbett, Graham, de Wit and Munster, as well as McLellan and many other researchers who have dedicated their careers to the study of infectious diseases, several vaccine candidates have already progressed to Phase 3 clinical trials, generally the final and most rigorous phase of testing, to see if they will work to prevent the novel coronavirus from taking hold in humans. On November 16, Moderna, the company partnering with the NIAID team, announced its initial findings that its vaccine was more than 94 percent effective at preventing COVID-19. It was the second after Pfizer to show such a hopeful finding.

Concludes Holland about his NIAID colleagues: “They were working on what we needed all along.”

By Erin Heath