AUSTIN, Texas - Researchers at Texas Biologics at The University of Texas at Austin, working with scientists internationally, have made an important discovery that could improve treatment of human cytomegalovirus (HCMV), a common but overlooked virus that poses serious risks to vulnerable populations, including people with compromised immune systems. According to the Centers for Disease Control and Prevention, the virus is the most infectious cause of birth defects in the United States.

The widespread virus - with global infection rates above 80%, according to some estimates - is hard to treat because it can evade the immune system. The research team, which includes leading scientists and engineers from the University of Freiburg and Cardiff University, developed a new type of antibody with a modified structure that can outsmart the virus and neutralize its ability to evade the immune system.

"Our engineered antibodies are like a lock that the virus can't pick," said Jennifer Maynard, a professor in the Cockrell School of Engineering's McKetta Department of Chemical Engineering and one of the lead authors on the new research published in Cell. "They retain their ability to activate the immune system but are no longer vulnerable to the virus's tricks."

Despite its prevalence, there is no vaccine for HCMV. Current treatments rely on antiviral drugs that can have toxic side effects and lead to drug resistance, creating an urgent need for safer and more effective therapies.

The virus spreads from person to person through body fluids. And like all herpesviruses such as canker sores and chicken pox, it stays in the body for life after infection.

In experiments, the antibody prevented the virus from spreading between cells, a key feature of HCMV that makes it so difficult to control. The antibodies significantly reduced viral dissemination in infected cell cultures, showing the ability to slow the spread of the virus.​

"It's like a tug-of-war between the virus and the immune system," said Ahlam N. Qerqez, lead author of the study, a former doctoral student in Maynard's lab, and now a senior scientist at Denali Therapeutics. "The virus has evolved clever strategies to pull antibodies away from their intended targets, making it harder for the immune system to do its job."​

The virus produces special proteins called viral Fc receptors (vFcγRs) that interfere with the body's natural defense mechanisms.​ These proteins bind to antibodies - immune system molecules that normally help fight infections - and prevent them from activating immune cells such as natural killer (NK) cells.​ NK cells are responsible for clearing out infected cells, but HCMV's vFcγRs essentially "hijack" antibodies, rendering them ineffective.​

The engineered antibodies are designed to avoid HCMV's vFcγRs while still activating NK cells to attack infected cells. ​

The team focused on a specific type of antibody called IgG1, which plays a key role in fighting infections.​ By studying how HCMV interacts with IgG1, the researchers identified the exact regions of the antibody that the virus targets and altered them to prevent the virus from binding.

For most healthy individuals, HCMV sits dormant and causes no symptoms.​ However, for people with weakened immune systems - such as organ transplant recipients, cancer patients and newborns - the virus can lead to severe complications, including organ damage, developmental delays and even death.​ HCMV is also the leading infectious cause of congenital birth defects, affecting up to 2% of pregnancies worldwide.​

The antibody engineering techniques developed by the team could be applied to other viruses that use similar immune evasion strategies, such as other herpesviruses and even certain bacterial infections.​ Additionally, the findings highlight the importance of targeting infected cells - not just the virus itself - in developing effective treatments.​

"This work represents a paradigm shift in how we think about antiviral therapies," said Jason McLellan, a professor in the College of Natural Sciences' Department of Molecular Biosciences at UT and co-author of the paper. "Instead of just trying to neutralize the virus, we're focusing on empowering the immune system to clear infected cells.​ It's a more holistic approach that could lead to better patient outcomes."

The engineered proteins will require several more rounds of testing before they can be used in clinical settings.​ The team is also investigating combining their approach with other therapies, such as antiviral drugs or vaccines, to create a comprehensive treatment strategy.

Other team members are George Georgiou, Sumit Pareek, George Delidakis, Amjad Chowdhury and Annalee W. Nguyen of the McKetta Department of Chemical Engineering; Alison G. Lee, Kelli Hager, Akaash K. Mishra, Mica Cabrera and Truong Nguyen of the Department of Molecular Biosciences at UT; Kirsten Bentley, Lauren Kerr-Jones and Richard Stanton of Cardiff University's School of Medicine; and Katja Hoffmann, Rebecca L. Göttler, Philipp Kolb and Hartmut Hengel of the University of Freiburg.