Dennis Burton, an immunologist at the Scripps Research Institute in La Jolla, California, who has developed a number of antibodies against HIV, agrees. “Obviously, the best thing of all is a vaccine. That’s a tried-and-tested method that carries very few risks. But if that doesn’t work, what’s our fall-back position?” he asks. “We have these antibodies, and we have them available now. If this works in humans, and that’s a reasonable supposition, you’d have something you can do now.”
Prolonged protection
Baltimore and his colleagues tested five different broadly neutralizing antibodies, one at a time, in mice with humanized immune systems. Two of the antibodies, called b12 and VRC01, proved completely protective — even when the mice received doses of HIV that were 100 times higher than a natural infection. After 52 weeks, the levels of antibody expression remained high, suggesting that a single dose would result in long-lasting protection. “We showed that you can express protective levels of antibodies in a mammal and have that expression last for a long period of time,” Baltimore says. “It sets the stage for human trials.”
Providing patients with periodic doses of these antibodies throughout their lifetime would be safer than coaxing antibody production from muscle cells, but it would be far from cost-effective. The gene-therapy approach, by contrast, recruits muscle cells to act as antibody factories and could be administered using a single intramuscular shot.
Experts in the field are cautiously optimistic. “Mice and monkeys don’t always tell the truth. It’s a really interesting idea, and it should be assessed in clinical trials,” says Wayne Koff, senior vice-president for research and development at the International AIDS Vaccine Initiative in New York. “Until someone shows that we can make these broadly neutralizing antibodies with a [classic] vaccine, I think this is an important concept that should be supported.”
But both Burton and Koff caution that gene therapy comes with its own set of problems. Because the antibody DNA is permanently inserted into the genome, there’s no way to turn it off if someone has an immune reaction against the antibodies. But it won't be known whether such side effects exist until the method is tested in people, something that Baltimore aims to do in the next few years. The researchers at the Children’s Hospital of Philadelphia, meanwhile, hope to get the first round of human trials of their technique started before the end of 2012.
