A new delivery method which uses a harmless virus to transport an antibody gene into human cells appears to have led to more than a year of antibody production in a new study testing the treatment against HIV.
A study team from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), virtually presented their findings at an oral presentation at the Conference on Retroviruses and Opportunistic Infections (CROI 2020
For more than a year, trial participants generated the Viral Research Center (VRC)-developed anti-HIV monoclonal antibody called VRC07.
“To the best of our knowledge, this marks the first time that an AAV-based technology to deliver an antibody gene has resulted in safe and sustained levels of that antibody in blood,” NIAID VRC director John Mascola, MD, said in a press release.
VRC07 is a broadly neutralizing antibody which has been shown to stop a wide variety of HIV strains in laboratory tests. The antibody was delivered using adeno-associated virus serotype 8.
The ongoing phase 1 clinical trial, known as VRC 603, aims to evaluate safety and tolerability of the virus delivered antibody treatment. The results presented at CROI 2020 included data on the first 8 participants.
The participants received a single dose of VRC07 and while continuing to take their daily antiretroviral therapy medication. There were 3 dose stratifications ranging from low to intermediate to high.
All participants produced VRC07 at detectable levels in blood tests. The production of VRC07 peaked 4 to 6 weeks after administration, decreased, and then began to increase again at about 16 weeks. The 3 volunteers who received the highest dose produced higher concentrations of antibody than the other groups.
In previous animal study, the virus-delivery system was able to provide genes for antibodies against simian immunodeficiency virus, the monkey equivalent to HIV. The monkey test subjects produced high levels of antibody and were protected from acquiring the virus.
“The concentrations of VRC07 observed in the study participants were lower than the antibody concentrations observed in animal studies of the AAV8-based technology,” NIAID officials noted.
There have not been any major adverse events thus far. Some participants reported mild tenderness at the injection site. Out of the 8 participants, 3 developed antibodies against the treatment, but it is not yet known if this would impact the effectiveness of the treatment substantially.
“Monoclonal antibodies hold enormous promise for preventing and treating both established and emerging infectious diseases,” Anthony Fauci, MD, director of NIAID, said in a press release.
“Novel delivery platforms such as viral vectors could facilitate the future development and deployment of antibody-based prophylaxis and therapy, and these findings are a promising first step in that direction.”
The study team continues to monitor the first 8 participants and enroll new volunteers in the trial.
The oral presentation, “Durable HIV-1 antibody production in humans after AAV8-mediated gene transfer,” was presented at CROI2020 on March 9, 2020.
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