Nashville, TN

How Nashville scientist Dr. Barney Graham began groundbreaking COVID-19 vaccine research decades ago

Dex Walker

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NASHVILLE, TN — Recent scientific advances enabled the coronavirus vaccines to be developed in just a few weeks instead of months or years. But this is not just an overnight success story. In fact, most of them have roots in the research of Nashville scientist Dr. Barney Graham and others at Vanderbilt University in the 1990s.

Present coronavirus vaccines were based on decades of research into other infectious diseases, like HIV. For years, scientists had tried to engineer a protein for HIV that would neutralize antibodies in patients. They haven’t succeeded in the experiment, but then Graham began applying protein engineering to Respiratory Syncytial Virus (RSV).

Graham and McLellan focused on working on the F proteins that stick out of the RSV. Graham immediately recognized that the precision in protein engineering could be used in developing vaccines for RSV and other enveloped viruses, including coronaviruses.

Coronavirus was becoming a threat to humans, starting with the SARS (Severe acute respiratory syndrome) outbreak in 2002 and MERS (Middle East respiratory syndrome) in 2012, which caused 40 percent fatality in those infected. Coronaviruses got their name from the spike proteins that cover the exterior.

After a little success with SARS and MERS, Graham and McLellan turned to the more common coronavirus, HKU1, and quickly stabilizing the spike protein. Despite their success, they struggled to get their research published.

“Everybody said, ‘Why are you working on coronaviruses? They just cause the common cold’,” Graham says.

Meanwhile, Graham was working on techniques to combat the mosquito-borne Zika virus. Along with the NIH colleagues, they worked rapidly to develop a vaccine delivered by DNA. They also partnered with a new Massachusetts biotech company, Moderna, that had developed quicker vaccines techniques. Rather than using DNA, the researchers use RNA to deliver the instructions for cells to make the same proteins.


Even though the vaccines were successful, the Zika epidemic had declined. In 2017, they worked together with Moderna to combine the precision antigen design with the mRNA delivery. They focused on the coronaviruses and paramyxovirus.

In early 2020, Moderna was ready to manufacture the Nipah mRNA and take it into a human clinical trial. But, on January 6, 2020, for the first time, the world was warned of the epidemic in Wuhan caused by a virus. Later, the whole world is in danger of getting the virus and is now caught in a worldwide pandemic.

On January 10, 2020, Chinese scientists released the genetic sequence of the virus, SARS-CoV-2. One day later, Graham and McLellan worked together in creating sequences to make the protein for solving structures and start a trial on immunizing mice.

While McLellan was revealing the atomic structure of the new spike, Graham provided a sequence for Moderna to begin manufacturing mRNA to be injected into mice.

“Even though we didn’t have any antibodies yet,” he says, “you could see the protein was in the right shape, and it was likely going to work.”

The first cases of COVID-19 had emerged in the United States back in 2020 and adding new urgency to their mission to produce vaccines as fast as possible in combating the coronavirus. The vaccine on animals stated showing efficacy, and they started to arrange to test the vaccine on humans. Neuzil and his team worked together in designing a trial of the first eight subjects in Seattle on March 16, followed by another 37.

“Within 41 days after we gave Moderna the protein sequence, they gave us back an mRNA product that could be put into people,” Graham said. “We did animal and human studies in parallel, at the same time, so we would always have the data we needed to start the next stage.”

“People say how could they make vaccines for corona so fast,” he says. “Well, they did it based on more than 30 years of research on RSV, HIV and MERS.”

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