Photo: Faith Ninivaggi
An adeno-associated virus produced by Guangping Gao, PhD, and colleagues at UMass Chan Medical School was used to deliver an HIV broadly neutralizing antibody that protected preclinical animal models from HIV. Published in Nature, these findings point to potential new approaches to protect young infants from perinatal HIV transmission.
“AAV is a very promising vehicle for delivering broadly neutralizing antibodies, such as the ones that protect against HIV transmission,” said Dr. Gao, the Penelope Booth Rockwell Chair in Biomedical Research, chair and professor of genetic & cellular medicine, director of the Horae Gene Therapy Center and director of the Li Weibo Institute for Rare Diseases Research. “By using a viral vector, we’re able to turn muscle cells into tiny biofactories capable of continuously pumping out protective antibodies for potentially years.”
Antiretroviral cocktails for HIV that include nevirapine, which prevents mother-to-infant transmission—also called perinatal transmission—are available but require patients to maintain regular dosages each day. Similarly, broadly neutralizing antibodies can be protective but levels deteriorate rapidly in the blood stream, requiring repeated infusions to maintain protection. Additionally, adults often develop anti-antibodies that cause their effectiveness to wane after repeated treatments.
New HIV infections among children have declined by more than 60 percent worldwide, but progress has stalled in recent years. Approximately 120,000 children acquire HIV each year globally, according to UNAIDS, a United Nations program.
Adherence to therapy can be challenging due to social and economic reasons as many patients lack access to regular medical care. A treatment that could be given once during a mother’s prenatal medical care has the potential to greatly reduce perinatal HIV transmission.
The biggest advantage of delivering immune proteins via AAV that protect against HIV is that the code to make the antibodies become imbedded in muscle cells at the injection site.
If delivered either prenatally to the mother or directly to a new born infant, the developing immune system learns to recognize the antibody as native and therefore is far less likely to develop anti-immune responses that typically occur with repeated exposure.
The next step for investigators will be a clinical trial in patients. Katherine Luzuriaga, MD, the UMass Memorial Health Care Chair in Biomedical Research, vice provost for clinical and translational research and professor of molecular medicine, pediatrics and medicine at UMass Chan, has received a $250,000 grant from the National Institute of Allergy and Infectious Diseases to plan a clinical trial to evaluate AAV-delivered antibodies in infants.
An infectious disease expert, Dr. Luzuriaga has led early-stage pediatric clinical trials resulting in licensing of multiple antiretroviral agents, including nevirapine in 1991. Her leadership of the first early combination antiretroviral therapy clinical trials in infants, along with characterization of the first case of HIV-1 remission in a very early treated infant, paved the way for current federal and WHO recommendations for very early infant diagnosis and lifetime combination antiretroviral therapy. Luzuriaga’s current efforts are focused on strategies to achieve long-term HIV remission in children off antiretroviral therapies.