An artificial protein was made in an experiment with four monkeys to see if the protein would be powerful enough to hinder if not stop the deadly virus, HIV from spreading throughout the body entirely. The results of the experiment were outstanding and more tests have been given since the experiment.
In test-tube experiments, eCD4-Ig outperformed all known natural HIV antibodies at stopping the virus from infecting cells, Farzan’s team reports in this week’s issue of Nature. To test how it works in animals, they then put a gene for eCD4-Ig into a harmless virus and infected four monkeys; the virus forces the monkey’s cells to mass produce the construct. When they “challenged” these monkeys and four controls with successively higher doses of an AIDS virus for up to 34 weeks, none of the animals that received eCD4-Ig became infected, whereas all of the untreated ones did.
The new study ups the ante on a similar gene therapy approach with natural antibodies that 6 years ago showed promise in monkey experiments, says an accompanying Nature editorial by AIDS vaccine researcher Nancy Haigwood of Oregon Health & Science University in Beaverton. “I am a huge fan of this paper,” Haigwood says. “It’s really very creative and a breakthrough as far as I am concerned.” Pediatrician Philip Johnson of the Children’s Hospital of Philadelphia in Pennsylvania, whose lab in 2009 showed success with a gene therapy that delivers an HIV bNAb, adds that eCD4-Ig “is a beautiful thing.”
Building on work by Johnson’s group, Farzan’s team stitched the gene for eCD4-Ig into an adeno-associated virus (AAV) that is harmless to humans. Those viruses, injected into monkey muscles, continued to produce eCD4-Ig for the 40 weeks of the experiment. “Everyone expects with AAV that this can go on forever,” Farzan says. The animals had no detectable immune response against the eCD4-Ig, presumably because it is so similar to pieces of their own cells.
Not everyone is convinced that eCD4-Ig will ultimately work better than natural HIV antibodies. Virologist David Baltimore, a Nobel laureate based at the California Institute of Technology in Pasadena, is working with a group developing its own AAV gene therapy that delivers an HIV bNAb. He describes the eCD4-Ig chimera and the paper as “impressive” and says he welcomes this new approach. But Baltimore, who like Johnson has already moved into early phase human trials with his gene therapy, notes that the new work offers only test-tube and animal data. “It’s perhaps a better construct than the antibodies we’ve been using, but it’s a matter of how it plays out in human trials,” Baltimore says. “I don’t think it’s easy to tell how that will happen.”
Who knows what will become of the HIV virus in say 10 or 20 years from now with the progression of this artificial protein and in future human experiments. Science is always conquering new viruses and illness puzzles of our day. Will the HIV virus be just another flu by then? How do you think human trials will compare with the monkeys? Let us know in the comments.