The search for a cure or vaccine for HIV hasn’t always inspired optimism—but hopes are buoyed now by recent advances, including a new understanding about how certain rare antibodies can fight the virus.
“There has been a substantial amount of research that has already been done” since scientists isolated some such antibodies in 2009 and 2010, says Ron Diskin, a biomedical researcher at the Weizmann Institute of Science in Rehovot, Israel, who recently visited the U.S. to share some of his findings and participate in a variety of HIV awareness efforts with the Consulate General of Israel in Los Angeles.
These antibodies, which occur in roughly 10 percent to 20 percent of people with HIV, are able to block many strains of the virus, which mutates rapidly and can therefore resist other antibodies produced by the human immune system. This special class of antibodies is therefore known as broadly neutralizing antibodies.
Researchers have known for some time that a small number of people with HIV produced broadly neutralizing antibodies, usually long after they were infected, even though these antibodies did not always prevent their disease from progressing. Scientists believe, though, that broadly neutralizing antibodies could be used in a vaccine to prevent HIV from taking hold in the first place. Some, including Diskin, think it could also eventually be used in treatment, replacing antiretroviral medications. Or, perhaps, human cells could be reprogrammed to produce the antibodies, he says.
Scientists isolated several new broadly neutralizing antibodies in 2009 and 2010, including one that can block more than 90 percent of the strains of the virus. Since then, researchers have been analyzing these agents to find out how they work—how they recognize and neutralize HIV, how the body produces them, and even how they can be made stronger.
In 2011, while doing postdoctoral research at the California Institute of Technology, Diskin was part of a team that modified an antibody called NIH45-46 to make it more effective in stopping HIV from entering cells. “We took something that was already extremely good and made it better,” he says.
Others pursuing research on broadly neutralizing antibodies include Rockefeller University, a partner with the Weizmann Institute; the National Institutes of Health; and the Scripps Research Institute, which has a partnership with the International AIDS Vaccine Initiative. Diskin emphasizes that what he is doing is “basic research” into the antibodies’ properties; it will be up to others to develop them into products that can then be tested, eventually, on humans. But that’s not necessarily far off, he says.
At left Ron Diskin
“In maybe three to five years we will have our first clinical data,” he predicts. And there is precedent—there are numerous antibody-based treatments for other diseases, primarily cancer, that are already in use. And various other types of basic research done by the Weizmann Institute have led to the production of many prescription drugs, such as Copaxone, used to treat multiple sclerosis. Indeed, the institute’s research has formed the basis for seven of the 25 most-prescribed drugs in the world, according to Weizmann officials.
At other institutions, recent advances in HIV antibody research include an NIH-funded study at Duke University that tracked how the virus and the strong antibody response evolved together in one HIV-infected person. This knowledge, according to the NIH, will help scientists in an effort to develop a vaccine that mimics the virus to generate broadly neutralizing antibodies, first in uninfected animals and then in uninfected people.
Whatever type of vaccine is developed, Diskin says, it may turn out that one dose is not enough to keep HIV at bay; “booster shots” may be needed. He also thinks antibody-based treatment might be able to replace antiretroviral drugs in suppressing the virus, not for all patients, but perhaps for some. “That’s a very interesting possibility,” he says.
Diskin, a native of Jerusalem, has been involved in HIV antibody research since 2010, having entered the effort at Caltech before joining the Weizmann Institute in September 2012. He had not thought of going into the field, he says, until Caltech biology professor Pamela Bjorkman asked him to join her lab’s effort. “I realized that would be a perfect project for me,” he says, as it’s culturally relevant and has the potential to make a significant impact.
Before visiting Los Angeles, Diskin attended the AIDS Vaccine Conference in Barcelona, Spain, where he was encouraged to see so much research being pursued so enthusiastically. “I’m overwhelmed with the amount of research that was done and the achievements that have been made,” he says. One highlight of the conference was a report on a trial of a vaccine called RV144, which showed at least a modest degree of success in preventing HIV infection. This vaccine uses ordinary antibodies, not broadly neutralizing ones.
What’s more, he says, it was obvious that much research into broadly neutralizing antibodies was going on. Diskin says the effort involves both collaboration and cooperation among scientific institutions. “There is a lot of cooperation because the magnitude of the task is enormous,” he says. “There is a lot of competition, also. Competition is not necessarily a bad thing—it stimulates the field and forces people to be efficient.”
And he’s optimistic that the work will be productive. “We’re talking about a lot of time and a lot of effort,” he says, “but at least it seems we’re heading the right way.”