Saturday, 28 February 2015

Wall Street Journal: Molecule Shows Ability to Block AIDS Virus

Approach has yet to be tested in humans but could lead to new treatments and a vaccine

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A new study could lead to the first step in new treatments for patients with AIDS and an alternative to a vaccine against HIV. Scripps Institute’s Michael Farzan explains. Photo: AP

By BETSY MCKAY, Updated Feb. 18, 2015 3:29 p.m. ET, 74 COMMENTS

Scientists have engineered a molecule they say can block infection with the virus that causes AIDS, a discovery that potentially could lead to a new therapy for patients as well as an alternative to a vaccine.

Researchers have been trying for three decades to develop an effective vaccine against the human immunodeficiency virus, which causes AIDS. They are also searching for a way to cure infected people. But the ever-evolving virus has eluded them.

Now, a team from the Scripps Research Institute and other institutions said it has identified a way to prevent HIV from infecting cells, using an approach that resembles gene therapy or transfer rather than eliciting an immune response.

HIV normally invades cells through two receptors. The new protein blocks the points where the virus binds to both cellular receptors, leaving no point of entry. Because it attaches to both receptors rather than just one, the protein, called eCD4-IG, blocks more HIV strains than any of several powerful antibodies that have been shown to disable the virus, the researchers said. The study waspublished online Wednesday by the journal Nature.

“It is absolutely 100% effective,” said Michael Farzan, a professor of infectious diseases at the Scripps Research Institute in Jupiter, Fla., and lead author of the study. “There is no question that it is by far the broadest entry inhibitor out there.”
Lead author Michael Farzan, right, with Matthew Gardner in Dr. Farzan’s lab at the Scripps Research Institute on Wednesday. PHOTO: ROLANDO DIAZ FOR THE WALL STREET JOURNAL

The approach has been tested only on four rhesus monkeys, not humans.

“This innovative research holds promise for moving us toward two important goals: achieving long-term protection from HIV infection, and putting HIV into sustained remission in chronically infected people,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which funded the work.

Scientists not involved with the work said it shows promise and should move into human testing quickly. An estimated 35 million people are infected with HIV, but only 13.6 million receive drug treatment that controls the amount of virus in their bodies, keeping it from multiplying and allowing them to lead relatively normal lives.

“It’s very clever and very powerful,” said Nancy Haigwood, an HIV researcher at Oregon Health and Science University, who wasn’t involved in the study but wrote about its potential as a vaccine alternative in a commentary in Nature. “This is going to be much better than any vaccine on the horizon.”

The scientists created the protein by fusing together elements of both cellular receptors to which HIV binds. They then injected genetic material encoding the protein into the quadriceps of the four monkeys, stimulating production of the new molecule.

The researchers infected the monkeys with a hybrid version of HIV, administering up to four times the amount of virus it took to infect a control group. The protein protected the monkeys for 40 weeks.

Dr. Farzan said the monkeys remained infection-free even when given 16 times the amount of virus that it took to infect the control group in experiments conducted after the study was completed.

He said he hoped human trials could begin within a year, after more testing in animals that is already under way. The first step, he said, would be to gauge the ability of the molecule to keep virus levels in HIV-positive people in check.

“We believe our goal now is to show it can work therapeutically,” he said.

The next step would be to test its efficacy as a vaccine, in people who don’t have the virus but are at high risk of infection, Dr. Farzan said.

The work builds on a 2009 study that proposed using gene transfer as an alternative to a traditional vaccine for HIV.

Philip Johnson, a professor at the University of Pennsylvania and director of the Children’s Hospital of Philadelphia Research Institute, who led the work this study builds on, said the new research offers promise for that concept.

“It appears to be an extraordinarily potent molecule,” he said. “It’s further validating of the idea that we should be thinking in alternate terms about how to attack HIV vaccines.” He said it should be tested in humans right away: “To me the non-human primate data are outstanding.”

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