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UT Austin-based vaccine research advances the fight against another deadly virus

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

“We have investigators at UT working not only on the current pandemic but also trying to evolve,” said Jason McLellan, professor of molecular biological sciences at UT’s College of Natural Sciences. Interventions for other virus families may cause outbreaks one day.

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

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

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

More than six years of pre-pandemic biomedical research on methods such as structural virology and spike protein stabilization prepared him for the breakthrough.

“When SARS-CoV-2, the causative agent of COVID-19, emerged in early 2020, we were able to rapidly translate all of our previous research,” says McLellan.

The fight against CCHFV

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

The researchers work in the McLellan Laboratory located in the Norman Hackerman Building on UT’s campus. (KXAN / Megan Fee Photo)

Tick-borne diseases are fatal in up to 30-40% of recorded cases. That’s why the World Health Organization has identified the virus as one of its top priorities for research and development.

“This disease is pretty terrible, it’s deadly, and it’s endemic to humans,” said Akaash Mishra, a PhD student in McLellan’s lab and first author of the recently published CCHFV. a large part of the world. scientific manuscripts.

According to the World Health Organization, the virus is transmitted to humans when bitten by a tick or by contact with the blood of an infected animal. Person-to-person transmission can occur through close contact with the bodily fluids of an infected person.

The majority of cases occur in people associated with the livestock industry, especially agricultural workers, abattoir 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 disease progresses, the hemorrhagic stage causes bleeding in various organs.

Structures of CCHFV. (Allowed: Akaash Mishra)

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

Mishra said that although the number of cases from these areas is rarely available, “several thousand” infections have been reported annually in recent years.

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

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

The endemic zone in which CCHFV exists has expanded over the past few years, scientists say.

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

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

A recent outbreak in Spain resulted in one death, and vectors for ticks have emerged in neighboring countries in the region, such as Italy.

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

“CCHF is mostly localized abroad, but as climate change hits, as bird populations change, ticks start to spread to other areas,” McLellan said.

While the virus may seem far-fetched, infectious disease experts in Austin say preparation is key when it comes to fighting priority pathogens.

“A few years ago, even for coronaviruses, we didn’t know they would cause such a global pandemic. So it’s important that we be prepared for emerging viruses that could be a potential threat in the future,” said Mishra.

The role of structural virology

Mishra started with a Ph. thesis on CCHFV when he joined the lab in 2018.

That’s when he started working on structural virology – a technology he said was “essential” in the development of vaccines for many viruses.

Defined in a UT press release as “the use of sophisticatedly detailed imaging of viral components to find their weaknesses”, structural viruses involve determining the atomic structure of the virus. three dimensions of the virus.

This approach gives scientists the information they need to design improved small molecules, vaccines and antibody treatments.

Structural virology has been used in efforts to develop vaccines against HIV, influenza and respiratory syncytial virus (RSV), Mishra said.

Stabilize spike protein

Another key component of McLellan Laboratories research has focused on identifying a method for stabilizing mutant proteins.

McLellan explained that the mutant protein on the surface of the coronavirus wants to change shape to infect the host.

By engineering, one way to prevent it from changing shape – locking the protein in a preliminary form – researchers are looking to develop a vaccine.

McLellan said he and his students began working on a stable method in 2013. Three years later, they’ve made great progress while working on a vaccine for the Middle East respiratory syndrome coronavirus.

All the viruses studied in McLellan’s lab before CCHFV, Mishra explained, were “type I” fusion proteins. These proteins are trimeric in their preliminary state.

Image of protein crystals – a CCHFV fusion protein in complex with neutralizing antibodies. (Allowed: Akaash Mishra)

Mishra says CCHFV is the first CCHFV to be studied in the McLellan Laboratory, because it’s a “type II” fusion protein. In contrast, these proteins form triplets from monomers on the viral surface when conformational changes from pre-transfection to post-transfection.

The main difference between “class I” and “class II” is how virus families develop.

He said his team’s breakthrough from studying CCHFV could be applied to other related viruses with different fusion proteins.

“Honestly, it is inspiring to witness history unfold right in front of your eyes,” Mishra said. “Not many 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 research team includes McLellan and other academic laboratories, biotech companies and the US Army’s Institutes of Medical Research on Infectious Diseases, according to a press release.

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

McLellan’s research was further supported by the Welch Foundation, a private source of funding for chemistry research at educational institutions in Texas.

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

McLellan says a lot of what scientists are learning and growing in his lab could be used to fight other priority pathogens in the future.

“It’s been really exciting to see research from the lab – from the couches behind me, from the students in the postdocs – to actually be translated into molecules that go into people’s arms,” ​​McLellan said. and impact on human health.

https://www.kxan.com/texas-coronavirus-vaccine/ut-austin-based-vaccine-research-propels-fight-against-another-deadly-virus/ UT Austin-based vaccine research advances the fight against another deadly virus

DUSTIN JONES

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