David Ho, MD, one of the scientists behind today’s successful antiretroviral cocktails, told a CUMC audience on June 28 that we are nowhere close to having a traditional vaccine against HIV, but an alternate approach using designer antibodies may be able to “passively” prevent HIV infection.
Ho, scientific director and CEO of the Aaron Diamond AIDS Research Center and the Irene Diamond Professor at The Rockefeller University, talked about his work on the new approach during the 2012 Cartwright Lecture, a major forum at CUMC featuring the world’s premier clinicians, medical scientists, and policy makers.
Ho said that until three years ago, the idea of using antibodies to prevent HIV infection was “simply out of the question. HIV antibodies did not latch on to the virus with a great deal of affinity.”
But recently a whole host of monoclonals has been isolated. “You can see now that the breadth against HIV [the percent of strains inhibited by these antibodies] ranges from 70 to close to 90 percent. This makes it now possible to think of prevention.”
Ho has just completed a Phase 1 trial of one antibody – ibalizumab – in uninfected individuals. “The antibody doesn’t interfere with binding, but it somehow blocks entry of the virus into the cell,” Ho said. “The safety is now shown, it is pretty well tolerated, and the pharmacokinetic profile is favorable for once a month dosing.”
Click on the image to watch the lecture (access limited to Columbia faculty, staff and students.)
Phase 2 trials to obtain more safety data over a longer time and with more patients will be conducted at Columbia and other centers soon.
But “ibalizamab has deficiencies that need to rectified,” Ho said. The antibody doesn’t work well against many strains of the virus and it is costly to produce antibodies. “The expense would be a serious challenge in the United States, and out of the question in the developing world.”
Ho’s lab is currently working on a modified version of the antibody, a fusion of ibalizamab with a portion of a newer antibody. “We’re getting fairly close to getting to the desired profile [of breadth, potency, and half-life], though we are not completely there yet,” he said.
His lab is also conducting animal experiments to see if gene therapy could be a cheaper way of delivering the antibodies. “Can we insert the genes for our antibody into muscle? Our experiments in animals so far suggest we could,” he said.
Though today’s antiretroviral therapies have turned HIV infection into a chronic illness for many infected people, “the epidemic continues to rage,” Ho said. “Thirty-three to 35 million people are currently living with a lethal infection, if left untreated, with another 2.5 million new infections per year. Needless to say, a vaccine is desperately needed.”