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Wall Street Journal
Search for AIDS Vaccine Advances
Betsy Mckay
January 5, 2012
Wall Street Journal - January 5, 2012

The quest for a vaccine against AIDS is gaining momentum, with research published Wednesday identifying promising new candidates that protected monkeys against a powerful strain of the virus and that soon could be tested in humans.

The study, published in the online edition of the journal Nature, also shed light on how the first human vaccine to have conferred limited protection against the AIDS virus may have worked.

In the research, several experimental vaccines partially prevented infection in monkeys from a highly potent, highly immune-resistant strain of simian immunodeficiency virus, an unusual finding, researchers said. SIV is similar to human immunodeficiency virus, or HIV, the virus that causes AIDS, and SIV infection in monkeys resembles HIV infection in humans.

The new vaccines, combining two different technologies to generate an immune response, reduced the chances that a monkey would be infected by the virulent SIV strain in each exposure by 80% to 83%, compared with a placebo. The vaccines also significantly reduced the amount of virus in the blood of monkeys who did become infected.

The protection was only partial - most of the vaccinated monkeys eventually became infected after multiple exposures. Still, the study was among the first to prevent infection against a virulent, highly immune-resistant SIV strain.

Plans are under way for clinical trials of a human-adapted version of one of the vaccines used in the monkeys, said Dan Barouch, professor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and lead author of the study. The vaccine will be tested in people both in the U.S. and internationally, including in populations in Africa where HIV infection rates are high, he said.

"There's more hope than ever before that an AIDS vaccine might be possible," said Dr. Barouch.

The findings are part of a renaissance in AIDS research, with multiple vaccine candidates under exploration and a landmark study published last year showing that AIDS drugs can reduce the spread of HIV from an infected person to others. But HIV researchers still don't fully understand how to prevent infection.

Vaccines, which work by spurring the body's ability to produce antibodies or immune cells, are considered the holy grail of AIDS research, because of the powerful role they played in eradicating smallpox and eliminating or sharply reducing the spread of other infectious diseases.

About 34 million people globally are infected with HIV, with about 2.7 million more infected each year, according to United Nations estimates.

In 2009, results of the first HIV vaccine to confer any protection against HIV were announced, after a large clinical trial in Thailand. That vaccine reduced the chances of infection only 31%, and prompted some controversy when one analysis found the results weren't statistically significant.

Still, the results helped rejuvenate the field. The latest study helps explain what many scientists suspected after the Thai trial: that the surface protein of the HIV virus, or its envelope, is involved in preventing infection.

"It clearly demonstrated you need to make antibodies against the outer coating of the virus," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, the part of the National Institutes of Health that oversees AIDS research and co-funded the latest study.

"It confirms what was seen in the Thai trial was real," said Louis Picker, associate director of the Vaccine and Gene Therapy Institute at Oregon Health & Science University, who reviewed the study led by Dr. Barouch but wasn't involved in it.

One strength of the study, said Dr. Fauci, was that the researchers made their vaccines with one strain of SIV and infected monkeys with another - replicating a likely real-world scenario, because the ever-mutating AIDS virus comes in many strains.

Many previous studies have used the same virus, but "that's not the way the real world works," he said. "There are so many different varieties of HIV out there. You've got to protect the person against potentially any strain." While monkey models are considered highly reliable in HIV research and the findings resemble those of the Thai trial in humans, HIV researchers cautioned that it won't be known whether these vaccines work in humans until they are tried.

"HIV is progressively revealing its secrets and each time it gets us closer to the goal, but this isn't like a basketball game where it's the last two minutes," said Bruce Walker, a veteran HIV researcher and director of the Ragon Institute, an enterprise of Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University. Ragon Institute helped fund the latest study and has raised $11 million of about $22 million needed for the clinical trials, Dr. Walker said.

Mark Schwartz, chairman and founding partner of MissionPoint Capital Partners, a private equity firm, donated $1 million of his own funds, together with his wife Lisa, toward the clinical trials. "Is it risky in a venture capital kind of way? Yes, it is," he said. But, he said," Ultimately, we think the real payoff is going to be in a vaccine." Write to Betsy McKay at betsy.mckay@wsj.com

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