AUSTIN (KXAN) – The same strategy used to create the COVID-19 vaccine is now helping researchers tackle yet another priority pathogen – and it all stems from research started here in Austin at The University of Texas.

“We have investigators here at UT that are working not only on the current pandemic, but also trying to develop interventions for other virus families that may one day cause outbreaks,” said Jason McLellan, professor of molecular biosciences in UT’s College of Natural Sciences.

McLellan demonstrates how his team determined the three-dimensional structure of the SARS-CoV-2 spike protein through a method called structural virology. (KXAN Photo/Megan Fee)

McLellan, who was named Texas Inventor of the Year back in June, played a crucial role in developing technology used to create the COVID-19 vaccine.

According to a UT press release, the vaccines from Pfizer, Moderna, Johnson & Johnson and Novavax all use the patented technology McLellan helped develop alongside his former postdoctoral researcher in 2017.

Over six years of biomedical research prior to the pandemic on methods like structural virology and spike protein stabilization prepared him for the breakthrough.

“When SARS-CoV-2, which is the causative agent of COVID-19, emerged at the beginning of 2020, we were able to just rapidly translate all of our prior research,” McLellan said.

The fight against CCHFV

Now, his team is using these same research developments to fight yet another deadly virus: Crimean-Congo hemorrhagic fever virus (CCHFV).

Researchers at work in the McLellan Lab located in the Norman Hackerman Building on UT’s campus. (KXAN Photo/Megan Fee)

The tick-borne illness causes death in up to 30-40% of documented cases. That’s why the World Health Organization identifies the virus as one of its top priorities for research and development.

“This disease is pretty terrible, it’s highly fatal and it’s endemic in a large portion of the world,” said Akaash Mishra, a graduate student in McLellan’s lab and the first author of the recently published CCHFV science manuscript.

McLellan describes the risks of Crimean-Congo hemorrhagic fever virus.

The virus is transmitted to humans by tick bites or through contact with infected animal blood, according to the WHO. Human-to-human transmission can occur as a result of close contact with the bodily fluids of an infected person.

The majority of cases have occurred in people involved in the livestock industry, especially agricultural workers, slaughterhouse workers and veterinarians.

According to the CDC, the onset of CCHFV is sudden, with initial signs and symptoms including headache, high fever, back pain, joint pain, stomach pain and vomiting. As the illness progresses, a hemorrhagic phase causes bleeding in different organs.

Structures of CCHFV. (Courtesy: Akaash Mishra)

CCHFV is found across Europe, throughout the Mediterranean and in parts of Asia, Africa and the Middle East.

Mishra said although case numbers from these areas are rarely available, a “couple of thousand” infections have been reported annually in recent years.

Turkey alone reports about one thousand causes each year, and the remaining infections are primarily concentrated in the Middle East and Balkan Peninsula.

The fatality rates vary from country to country, Mishra said. Turkey has reported rates between 3-9% of cases, while Afghanistan has reported deaths in 26-43% of cases.

Scientists said the endemic zone in which CCHFV exists has expanded over the last few years.

McLellan breaks down the components of the Ebola virus glycoprotein. (KXAN Photo/Megan Fee)

Mishra said a major concern is the spread of CCHFV to new European countries.

A recent outbreak in Spain resulted in a fatality, and infected tick vectors have appeared in countries neighboring the region, such as Italy.

International animal trading and ticks carried by migratory birds are other potential causes of the spread.

“CCHF is primarily localized overseas, but as climate change occurs, as bird populations change, the tick begins to spread to other areas,” McLellan said.

Though the virus may seem far away, infectious disease experts here in Austin said preparation is key when fighting priority pathogens.

“A few years ago, even for coronaviruses, we didn’t know they would cause such a global pandemic. So, it is important for us to be prepared with emerging viruses that may be future potential threats,” Mishra said.

The role of structural virology

Mishra started his Ph.D. thesis on CCHFV when he joined the lab back in 2018.

It was at that point he began his work on structural virology – a technology that he said has been “very essential” in developing vaccines for a variety of viruses.

Defined in a UT press release as “the use of exquisitely detailed imaging of viral components to find their weaknesses,” structural virology involves determining the three-dimensional atomic structure of a virus.

This method provides scientists with the information they need to design improved small molecules, vaccines and antibody therapeutics.

McLellan explains how structural virology works.

Mishra said structural virology has been used in attempts to develop vaccines for HIV, influenza and respiratory syncytial virus (RSV).

Mishra explains how structural virology has been used to tackle other viruses.

Stabilizing the spike protein

Another critical component of the McLellan Lab’s research has focused on determining a method of stabilizing the spike protein.

The spike protein found on the surface of the coronavirus wants to change shapes in order to infect the host, McLellan explained.

By engineering a way to prevent it from shape-shifting – locking the protein in its prefusion form –researchers are able to develop a vaccine.

McLellan explains the importance of stabilizing the spike protein.

McLellan said he and his students began working on a method of stabilization in 2013. Three years later, they made major progress while working on vaccines for the Middle East respiratory syndrome coronavirus.

McLellan demonstrates spike protein stabilization using 3-D models of the RSV spike protein.

All viruses worked on in McLellan’s lab prior to CCHFV have been “class I” fusion proteins, Mishra explained. These proteins are trimeric in their prefusion state.

 An image of protein crystals – a CCHFV fusion protein in complex with neutralizing antibodies. (Courtesy: Akaash Mishra)

Mishra said CCHFV is the first of its kind to be studied in the McLellan Lab, as it falls into the category of “class II” fusion protein. In contrast, these proteins form trimers from monomers on the viral surface when changing shapes from prefusion to postfusion.

The major difference between “class I” and “class II” is how the viral families evolve.

He said his team’s breakthroughs from researching CCHFV can be applied to other related viruses with different kinds of fusion proteins.

“It’s been very inspiring, honestly, watching history happen right in front of you,” Mishra said. “Not a lot of people get that opportunity during their PhD.”

Prometheus: The team behind the breakthrough

A research project called Prometheus is leading the fight against CCHFV.

The team is composed of McLellan’s and other academic labs, biotech companies and the U.S. Army Medical Research Institute of Infectious Diseases, according to a press release.

McLellan explains how the various contributors of Prometheus work together to fight priority pathogens.

Prometheus is funded by the U.S. National Institute of Allergy and Infectious Diseases.

McLellan’s research was additionally supported by The Welch Foundation, a private funding source for chemical research at educational institutions in Texas.

McLellan holds up a custom bobblehead gifted to him by David Vanden Bout, interim dean of UT’s College of Natural Sciences, at a recent celebration of his COVID-19 vaccine research. (KXAN Photo/Megan Fee)

McLellan said a lot of what scientists are learning and developing in his lab could be used fight other priority pathogens going forward.

“It’s been really exciting seeing research from the lab – from the benches behind me, from the students in postdocs – to actually get translated into molecules that are going into the people’s arms and are having an impact on human health,” McLellan said.