Jason McLellan stands in the McLellan Lab at The University of Texas at Austin in 2020. St. Clair Shores City Council issued a proclamation in McLellan’s honor for his work on the COVID-19 vaccine June 21.

Jason McLellan stands in the McLellan Lab at The University of Texas at Austin in 2020. St. Clair Shores City Council issued a proclamation in McLellan’s honor for his work on the COVID-19 vaccine June 21.

Photo provided by the University of Texas at Austin


St. Clair Shores native who helped develop technology for COVID-19 vaccine honored

By: Kristyne E. Demske | St. Clair Shores Sentinel | Published July 29, 2021

 McLellan, left, and graduate student Daniel Wrapp, work in the McLellan Lab in February 2020.

McLellan, left, and graduate student Daniel Wrapp, work in the McLellan Lab in February 2020.

Photo provided by the University of Texas at Austin

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ST. CLAIR SHORES — As a child in St. Clair Shores, Jason McLellan, Ph.D., knew he wanted to help people.

McLellan, who graduated from South Lake High School in 1999, said he had always thought he’d be a doctor because he wanted to help people. At Wayne State University, he excelled at chemistry and organic chemistry, which aren’t subjects many gravitate toward, he said.

“The professors took notice and asked me to work in their lab performing research in organic chemistry,” he said. “I loved it, working in the lab.”

He enjoyed it so much that, after publishing his first paper in organic chemistry, he switched his major from pre-med. Taking a graduate-level biochemistry class, he realized that subject fascinated him, as well. In 2003, McLellan graduated from Wayne State University and headed to Johns Hopkins University School of Medicine for graduate school, where he joined a structural biology laboratory that determines three-dimensional structures of proteins and other biological molecules.

It was that path that eventually led him to have an impact on the COVID-19 vaccines now being administered around the world.

“I was trained in a technique called X-ray crystallography,” he said. He likened it to growing rock candy, but with crystalized proteins instead. Doing so enabled him and the other researchers to be able to three-dimensional print a protein to see what it looks like and learn how it functions.

When McLellan was looking for where to do his post-doctoral study, he sought research that would have more real-life applications, to “get back to trying to help people more directly.”

That’s how he came to work with Dr. Peter Kwong at the National Institutes of Health in Bethesda, Maryland, where Dr. Anthony Fauci also works.

Kwong’s lab was part of the NIH’s Vaccine Research Center, focusing on structure-based vaccine design with the goal of developing an effective HIV vaccine.

“A lot of the traditional vaccines that we have ... they were created without much of a structural understanding of the virus or bacterial protein,” McLellan said. “That worked for many viruses and bacteria, but then you get a group that are more resistant.”

Researchers working with structure-based vaccine design seek to determine structures on the surface of the proteins of the virus, then isolate antibodies from human survivors and characterize them to see which are most potent against that particular pathogen. He and the other researchers then come up with a small group of the most effective antibodies, which they know humans are capable of producing, and develop structures to help them bind to a patch of the large protein of the pathogen.

“In the lab ... some of the viral proteins are like shape-shifting molecules. The best antibodies target Confirmation A, not Confirmation B. Then, we can engineer proteins in the virus to prevent it from (changing),” he said.

At first, he said he and the other laboratory researchers were working on development of a vaccine for HIV, but “a lot of what we were doing was failing.” They didn’t know if that was because they had bad ideas, or if HIV— which McLellan said changes much more than many other viruses — was just “too good” of a virus. So they switched to developing a vaccine for respiratory syncytial virus (RSV), a major childhood pathogen that lacks a vaccine and is the leading cause of hospitalizations in the U.S., where it also causes the death of many elderly patients, as well. Around the world, it is even more deadly for children.

“We were able to use structure-based vaccine design and design a molecule based on one of the surface proteins of RSV,” he said. McLellan designed a stabilized fusion protein that, when injected by the NIH lab of Dr. Barney Graham into mice and monkeys, produced very high levels of neutralizing antibodies that can fight the virus, 10-fold higher than what had been seen before. It was named one of the 2013 Top Ten Breakthroughs of the Year by Science Magazine and the vaccine molecule entered Phase 3 clinical trials in 2020.

McLellan left the Vaccine Research Center in 2013 to start an independent research lab at Dartmouth College. When the Middle East respiratory syndrome (MERS) emerged, “Barney and I thought, why don’t we try to apply structure-based vaccine design to coronavirus, because the spike protein (is) related to the fusion protein from RSV.

“We thought we could apply everything we had learned from RSV to coronavirus.”

Working with another group, they were able to determine the first three-dimensional structures of the coronavirus spike protein in 2016, and McLellan’s laboratory determined mutations to make to the protein to stabilize it and keep it in the pre-fusion confirmation. “That ended up working really well,” he said, with only two amino acid changes needed for the entire protein, which caused a “big boost to the amount of protein we could produce in the lab.”

The protein elicited the top immune response when tested on mice, and the teams discovered that, “although we were making changes, at that time, to the MERS coronavirus spike, it also worked with the SARS coronavirus.”

The means to stabilize coronavirus spikes in their pre-fusion confirmation dates back to 2013, and mRNA technology was developed as early as 2002, he said.

“Although these vaccines were created very quickly, all the technology that went into it were created about a decade before,” McLellan said of the COVID-19 vaccines being administered around the world. “It didn’t just happen, but it was a convergence of things, where the mRNA platform, it can encode for different proteins. That’s why it’s so fast. We don’t have to retest everything.

“There (were) already 10 different mRNA vaccines being tested in people before these coronavirus vaccines. (We) already knew how they behaved, how safe” they were.

By the time 2020 dawned, McLellan — who moved his laboratory to the University of Texas at Austin in 2018 — and other researchers knew the emerging beta coronavirus similar to SARS was the pathogen.

“All we needed was the sequence of the spike protein to put the same two stabilizing” amino acids in place, he said. Chinese researchers posted the sequence Jan. 10, 2020, and “the next day, we had already designed where to put the stabilizing mutations, and Barney was in contact with Moderna, telling them this is where you put the code,” McLellan explained.

The design McLellan helped to develop was used in the vaccines created by Johnson and Johnson, Moderna, Pfizer and Novavax. He said they also worked with Eli Lilly to create the antibody treatment to treat COVID-19.

McLellan said he was surprised when he learned the St. Clair Shores City Council was issuing a proclamation in his honor.

“I’m very grateful for their acknowledgement, and I was very excited my parents got to attend and say some words on my behalf,” he said. “I know they were really excited on my behalf.”

His mother, Karen McLellan, said she and her husband both grew up in St. Clair Shores and attended South Lake High School, just like Jason McLellan. They now live in Chesterfield Township.

“He always wanted to be a pediatrician, for as long as I can remember,” she said. “It changed when he went to Wayne State. Some of the professors took him under his wing, got him into his labs there. That started him on his trajectory.”

She said she and her husband were not surprised that their son’s work has made such an impact.

“He’s very dedicated in his work, a very smart child,” she said. “We are so proud to be his parents. I tell him that all the time.

“It did not surprise me. He has done really well.”

In issuing the proclamation June 21, Mayor Kip Walby said McLellan’s work and accomplishments were outstanding.

“We’re proud of him. It’s unbelievable, quite frankly,” he said.

McLellan said the work on coronavirus vaccines hasn’t ended.

“Since then, we’ve created the second-generation spike protein that’s even more stable (and is) being tested in low- and middle-income countries now as a vaccine,” he said. “It is surreal.

“It’s been rewarding. It’s a huge effort to make these vaccines. We played a small part, but it’s been terrific for a lot of people in the lab.”

McLellan credited the nonstop work of his graduate students in the early hours of 2020 as they raced to adapt the technology for the vaccines.

“It’s been a devastating pandemic, millions of lives lost, but we are happy about seeing contributions from the lab going to make the vaccines,” McLellan said.

What saddens him, he said, is how the vaccines have become politicized.

“It’s a triumph of science to create a vaccine in 10 months. These are incredibly safe vaccines. We have huge portions of the population who want nothing to do with them, and it’s bizarre,” he said. “There’s a lot of it in Michigan. My family’s still there. I have relatives who won’t take it.

“It is a bit disheartening.”

His lab is working to develop a universal vaccine that will protect against the different variants of SARS, as well as the coronaviruses that haven’t emerged yet, “that are still in bats, that might someday jump species.

“It’s a high bar,” he said.

They continue to apply structure-based vaccine design to different viruses, bacteria, parasites and other pathogens.

“It’s been busy, but it’s been exciting, and it’s kind of my dream seeing things from the lab go into humans and have a positive effect,” he said.

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