Scientists Spot New Antibodies Against HIV, Opening Up Potential Path to AIDS Vaccine
Scientists have never been able to make an effective AIDS vaccine, largely because the HIV virus is crafty, always finding ways to mutate and escape the body’s immune defenses. But now a national team of scientists has found antibodies that zero in on newly identified weak spots in the virus, potentially opening up promising new pathways for the development of an AIDS vaccine.
Researchers are reporting today in the journal Nature that they have discovered 17 novel antibodies that are all capable of neutralizing a broad spectrum of HIV strains, by hitting precise regions on the virus that are genetic common ground, no matter how many wily mutations the virus may make. The findings are being published by a team of scientists from Theraclone Sciences, a private biotech company in Seattle; The Scripps Research Institute in San Diego; South San Francisco-based Monogram Biosciences, a unit of Lab Corp of America (NYSE: LH); and the New York-based International AIDS Vaccine Initiative (IAVI).
The latest findings build on work this same team published two years ago in Science, when they identified two genetically engineered antibodies to hit two weak spots on the HIV virus. By finding so many more structural vulnerabilities in the virus, researchers now hope to take the next step by crafting compounds that can spur the body to make these antibodies, hitting the viral equivalents of Achilles’ heel. If this idea can be proven in future clinical trials, it could pave the way for the first vaccine against a disease that still kills an estimated 1.8 million a year around the world, according to UNAIDS.
“The more you understand the virus and characterize it, the better you can do at designing immunogens [ingredients for vaccines],” said Kristine Swiderek, the vice president of research at Theraclone. “It’s very exciting.”
Dennis Burton, a professor of immunology at Scripps and a lead author of the study, added in a statement that, “because of HIV’s remarkable variability, an effective HIV vaccine will probably have to elicit broadly neutralizing antibodies. This is why we expect that these new antibodies will prove to be valuable assets to the field of AIDS vaccine research.”
The far-flung collaboration of scientists got its start in a pretty basic observation from sub-Saharan Africa, where AIDS causes the most damage. Scientists there have long noticed that a few rare people can get infected with HIV, yet somehow retain robust immune defenses so they never get sick. IAVI and its collaborators have worked on clinical protocol to identify these special people and collect blood samples from them, which served as the essential raw material of this research collaboration.
IAVI, a global nonprofit supported by the Bill & Melinda Gates Foundation, provided the financial support for the collaboration with Scripps, Theraclone, and Monogram. Each of those parties played a distinct role, Swiderek says. Theraclone used its proprietary technology to produce the novel antibodies that could bind specifically with regions on the virus known as epitopes. The team at Monogram ran the screening tests of those antibodies against various strains of HIV in the lab. And the scientists at Scripps and IAVI worked together on characterizing those precious regions of the virus that are now thought to have potential as vaccine targets.
In the early days of the collaboration, Swiderek says the team worked on samples from just one individual donor, which yielded the first two antibodies described two years ago in Science. Emboldened by that progress—which marked the first time in a decade that any broadly neutralizing antibodies had been discovered—the team continued looking at more samples gathered by IAVI. This latest work being published in Nature, with the 17 new antibodies, is based on the contributions from four more HIV-resistant people from Africa, Swiderek says. The scientific collaborators are working on making antibodies against samples from one more donor, which isn’t yet reflected in today’s paper in Nature, she says.
The business opportunity in HIV is always one for ethical debate—how treatments should be priced, and how best to provide access. Merck has tried and failed to develop an AIDS vaccine, and there have been many efforts in government labs, with money from nonprofits like IAVI, to continue the vaccine hunt.
Companies like Foster City, CA-based Gilead Sciences, GlaxoSmithKline, Merck, and others have long proven there’s a big business in the treatment of HIV in wealthy countries where people can afford to take antiretroviral medications on a chronic basis. More than 30 such HIV drugs have been approved for sale by the FDA, and although it’s been tried, none have been shown to work like a preventive vaccine. The market for AIDS drugs, not counting any vaccine, is estimated to reach $13.7 billion by 2016, according to the market research firm GlobalData.
Under this particular collaborative agreement, IAVI owns the rights to all the antibodies for the development of an AIDS vaccine, while Theraclone retains the commercial rights to the broadly neutralizing HIV antibodies for therapeutic purposes, according to Russ Hawkinson, Theraclone’s vice president of finance. If Theraclone decided to pursue that route, it would have to make the bet that certain AIDS patients would be better candidates for an injectable therapy that could conceivably be taken, say, once a month. That would be in contrast to today’s standard antiretroviral drugs, which are mostly taken as once-daily pills. No one has come up with such an antibody-based therapy for HIV for commercial use, but Theraclone said it has been having ongoing talks with potential pharmaceutical partners.
The latest HIV work may never lead to a viable product candidate, but it’s the kind of thing that could help boost the reputation of its technology, and its potential for making other kinds of antibodies. Theraclone has a partnership with Japan-based Zenyaku Kogyo to develop broadly neutralizing antibodies for flu, and an alliance with New York-based Pfizer to make antibodies against various infectious diseases and cancer. Theraclone plans to start a clinical trial of its lead antibody for flu by the end of this year, and to begin another trial of an antibody for cytomegalovirus infections in the first half of 2012, Hawkinson says.