IAVI welcomes the promising results that Michael Farzan and his team have achieved by constructing an artificial protein that potently blocked HIV and SIV in vitro and protected against SHIV challenge in monkeys.
These findings complement other ongoing studies aimed at designing prevention approaches that can work across the enormous diversity of HIV, and further demonstrate the potential promise of immunoprophylaxis to prevent and control HIV infection using an adeno-associated vector (AAV) for delivery.
As with all HIV prevention research, the key question will be if the approach will be safe and effective in people. HIV is a wildly mutating virus, and its prevention is made even more challenging by the fact that approaches that show promise in animals may not always work in humans.
IAVI is among the school of HIV research experts who see broadly neutralizing antibodies (bNAbs) as having the greatest potential to prevent HIV infection; we conduct and support approaches to induce bNAbs in the body through vaccination and other routes. bNAbs identified in people living with HIV have shown the ability to neutralize the vast majority of circulating HIV strains (up to 90% for the broadest) and have prevented infection in animal studies.
Recent breakthrough discoveries have enabled identification and characterization of new targets for bNAbs on HIV’s surface and the design of vaccine candidates to elicit bNAbs. Early clinical testing of a candidate for a broad and long-lasting vaccine is anticipated to begin within the next few years.
Meanwhile, based on promising results in laboratory and animal studies, human Phase I trials are currently seeking to demonstrate the value of bNAbs in people. One trial uses a strategy pioneered by Phil Johnson at Children’s Hospital of Philadelphia, in collaboration with IAVI, to induce bNAb production in muscle cells, using a prototype candidate that delivers a gene of a bNAb (PG9) through AAV-1. Results are anticipated later this year.
The Farzan non-human-primate study represents a similar approach but uses a synthetic antiviral protein (eCD4-Ig) instead of a bNAb. Individual bNAbs generated at the IAVI Neutralizing Antibody Center at The Scripps Research Institute as part of IAVI’s Protocol G were among those used to compare the neutralizing and protective activity of each of these bNAbs and the gp120-binding construct eCD4-Ig generated by Farzan and colleagues.
“The new study reinforces the potential promise of the AAV-mediated immunoprophylaxis approach as an alternative to vaccination to prevent HIV infection,” said Wayne C. Koff, IAVI Chief Scientific Officer. “We look forward to further studies that will show how well any of these approaches can work in humans and will bring us all closer to a world without HIV/AIDS.”