A University of Miami Miller School research team has found a new approach to preventing and treating HIV infection in a preclinical model. With one injection of anti-HIV monoclonal antibodies, the researchers were able to suppress the virus for three years in one monkey and for extended periods in two others.
“Our goal is to be able to deliver these potent broadly neutralizing antibodies with one shot so the patient is good for life,” said Ronald C. Desrosiers, Ph.D., professor of pathology and a longtime HIV researcher. “But more research needs to be done.”
Dr. Desrosiers is the corresponding author of a new Miller School study, “Adeno-Associated Virus Delivery of Anti-HIVMonoclonal Antibodies Can Drive Long-Term Virologic Suppression,” published March 6 in the journal Immunity. Miller School co-authors were Jose M. Martinez-Navio, Ph.D., and Sebastian P. Fuchs (both co-first authors), Shara N. Pantry, Ph.D., William A. Lauer, and Natasha N. Duggan.
The study was conducted in collaboration with the Wisconsin National Primate Research Center, University of Wisconsin–Madison, the Frederick National Laboratory for Cancer Research in Maryland, and the Gene Therapy Center at the University of Massachusetts Medical School.
While anti-retroviral drug therapy of HIV-infected humans, or SIV– or SHIV-infected monkeys, may suppress viral replication, it is not a cure, according to the study’s authors. Removal of antiviral drugs results in a rebound of plasma viral loads in the vast majority of individuals. While prior studies have shown that antibody therapies can suppress the virus to some degree, repeated infusions are needed to maintain a protective concentration.
In their new study, the Miller School researchers used an adeno-associated virus (AAV) to deliver gene products into the muscle cells, turning them into cellular “factories” that can produce the genetically engineered antibodies indefinitely, Dr. Desrosiers said.
One of the study monkeys had the most positive response to the new approach. After receiving a single injection of the AAV-delivered antibodies, its HIV viral load immediately dropped below the limit of detection, and has remained undetectable for more than three years.
“Our study provides a proof of concept that this approach can deliver a functional cure for HIV,” Dr. Desrosiers said.
While two other monkeys in the study also maintained long-term viral suppression, the AAV delivery strategy triggered a defensive immune system response that inactivated the antibodies, according to Dr. Desrosiers. The muscle cell-produced antibodies were seen as foreign antigens, resulting in an anti-drug reaction, which can also occur in some patients receiving antibodies for treating Crohn’s disease, rheumatoid arthritis or other conditions.
“Now, we have to solve this anti-drug antibody problem so that so that we can generate a robust response in virtually all humans,” said Dr. Desrosiers, who is focusing his research on this challenging issue. “One advantage to this AAVapproach is that it could be readily applied throughout the developing world, where antiretroviral therapies are not readily available. An easy ‘one-shot’ approach could make a huge difference in addressing this global epidemic.”
Miller School of Medicine