Researchers develop antibody to combat HCMV, a common, overlooked virus
· News-Medical"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.
Jennifer Maynard, Professor, Cockrell School of EngineeringThey retain their ability to activate the immune system but are no longer vulnerable to the virus's tricks."
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.
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