Researchers use innovative gene therapy approach in model development
San Antonio, Texas (September 9, 2020) – Hepatitis B is a liver disease affecting more than 300 million people worldwide, and researchers recently identified a new aid in the quest to create better therapeutics. Squirrel monkeys have been identified as a new animal model to further study and improve therapies for hepatitis B infection caused by the hepatitis B virus (HBV). This discovery has been five years in the making at Texas Biomedical Research Institute (Texas Biomed). Chimpanzees were previously the preferred animal model to study hepatitis infections; however, in 2015 chimpanzees were no longer available for use in biomedical research. Texas Biomed focused its efforts on finding a suitable replacement model that can produce chronic infection, aiding in the development of new therapies. Christopher Chen, Ph.D., Assistant Director for Research at the Southwest National Primate Center, led the team of scientists who published their findings in Hepatology Communications.
“Texas Biomed previously discovered woolly monkeys were natural carriers of a HBV monkey virus that had a similar genetic sequence to the human virus, which was a significant finding that provided a clue that led us to where we are today,” Dr. Chen said. “With our approach in this study, we were able to directly infect the liver and prolong infection for up to 6 months. This is the longest infection period among any of the current HBV models and is critical for when we eventually test therapeutics to treat prolonged infection.”
Texas Biomed has a storied history in researching HBV. Professor Emeritus Dr. Robert Lanford was instrumental in early studies that led to the development of the pediatric HBV vaccine and Hepatitis C cure using chimps. He also discovered the woolly monkey hepatitis virus to further study human HBV, but woolly monkeys are endangered animals, like chimpanzees, and cannot be used in biomedical research. Dr. Chen was able to take this discovery several steps further using his expertise in gene therapy. He incorporated the HBV genome into an adeno-associated virus (AAV), a non-pathogenic virus that readily infects liver cells. Once the liver cells are infected, they produce infectious woolly monkey HBV, not AAV.
“AAV is like a Trojan horse and is good at getting into the liver. To improve delivery of the woolly monkey HBV genome, our strategy was to use this alternative viral gene delivery approach. It was a more efficient approach than just using the woolly monkey HBV to cause infection,” Dr. Chen said. “We’re also using this approach to develop models for liver cancer.”
Dr. Chen and his team observed a sustained infection that was detectable for six months. To prolong and increase the level of virus in the bloodstream (viremia), future work will focus on adding an immunosuppressive agent prior to and during early infection. Higher sustained viremia will increase the utility of the model in the development of new therapies.
While HBV impacts 300 million people, the greatest at risk are infants, who can become infected with the virus through mother-to-child transmission during delivery. According to the Centers for Disease Control and Prevention, infants who are not properly vaccinated during the first few months of birth are 90% likely to develop chronic HBV, leading to liver disease and cancer. Although there’s no cure, adults are also encouraged to receive the HBV vaccine if they’re at risk of exposure. Current therapies suppress the virus and need to be taken daily.
“HBV is really hard to cure. The goal with this new model is to use it to test new curative treatments,” Dr. Chen said. “To do that we will need to continue to improve the model, so it can support higher viremia over longer periods of time.”
This investigation used resources supported by SNPRC’s grant P51 OD011133 from the Office of Research Infrastructure Programs, National Institutes of Health.
Texas Biomed is one of the world’s leading independent biomedical research institutions dedicated to eradicating infection and advancing health worldwide through innovative biomedical research. Texas Biomed partners with researchers and institutions around the world to develop vaccines and therapeutics against viral pathogens causing AIDS, hepatitis, hemorrhagic fever, tuberculosis and parasitic diseases responsible for malaria and schistosomiasis disease. The Institute has programs in host-pathogen interaction, disease intervention and prevention and population health to understand the links between infectious diseases and other diseases such as aging, cardiovascular disease, diabetes and obesity. For more information on Texas Biomed, go to www.TxBiomed.org.