The team engineered the immunoadhesin sequences into the AAV vector and injected the constructs into the muscles of nine rhesus macaques, where the muscle cells then started to produce the chimeric antibodies and secrete them into the bloodstream. After four weeks, the team infected the monkeys with SIV and monitored their health along with antibody and virus levels in their blood over one year. Six of the nine macaques showed no sign of SIV infection, and the remaining three did not develop AIDS during the course of the study. In contrast, six control monkeys all became infected, and four of them died before the experiment finished.
The results are “really encouraging,” says Andrew Sewell of Cardiff University’s School of Medicine in the U.K., who was not involved in the study. “I have not seen anything that worked this well before.”
“This has given us a really big green light in the monkey model, but of course we still need to show this also works in humans,” says Johnson. There are four potent antibodies that work against HIV, and it may be possible to use the AAV vector to deliver the necessary genetic sequences for the antibodies in humans. Johnson hopes to get permission to start clinical trials soon and is optimistic that the technique can be adapted to humans. If successful, he says, it could turn into an affordable way to protect against HIV.
“The manufacturing technology available today makes it possible to do this at a very accessible cost,” Johnson says. “Having said that, at this point, the field is looking for anything that works, no matter what the cost; we just need something that works, full stop.”
“The data from this study show the promise of vector-mediated gene transfer as an approach for immunization,” says Pat Fast, chief medical officer at the International AIDS Vaccine Initiative. “We plan to collaborate with Doctor Johnson to expand on the monkey studies and to support the optimization of the vector for eventual testing in humans.”
Sewell shares this optimism: “If you think of HIV as an Achilles that can only be attacked by its heel, this is a designer weapon that can go straight to the heel. The fact that it works so well in macaques is very promising.”
Johnson and Sewell both caution, however, that it will be important to find more antibodies to keep HIV in check. “We may want to put in two or more effective antibodies at the same time to put additional pressure on the virus, so the more good antibodies we can find, the better,” Johnson says.