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Crucell Vaccine Stops AIDS in Monkeys, Harvard Scientist Says

By Simeon Bennett

Nov. 9 (Bloomberg) -- Crucell NV's experimental AIDS vaccine kept six monkeys from getting an animal equivalent of the disease, suggesting a decades-long search for ways to stop the deadly infection isn't yet at a dead end.

Researchers from Leiden, Netherlands-based Crucell and Beth Israel Deaconess Medical Center in Boston reduced levels of simian immunodeficiency virus, or SIV, in the monkeys as much as 250-fold and held off AIDS for more than 500 days, according to a report in the online edition of the journal Nature. They're now testing a similar form of the vaccine in 48 healthy people.

Last year, a vaccine being developed by New York-based Merck & Co., which had also appeared to benefit monkeys, failed in human testing. The problems appeared linked to a cold virus in the vaccine, which unexpectedly raised people's risk of getting AIDS. While the initial Crucell-Harvard vaccine recipe won't be used in humans because it contains the same cold virus, it does offer some promise, said Dan Barouch, the lead author and a virologist at Harvard University and Beth Israel.

``Our new data suggests we're not at the end of the road when it comes to vaccine development,'' he said in a Nov. 7 telephone interview.

Crucell is a biotechnology company that markets vaccines and antibodies to treat infectious diseases such as influenza, hepatitis A and B, and typhoid fever. The company's best-selling product is Quinvaxem, a liquid vaccine co-developed with Basel, Switzerland-based Novartis AG and launched in 2006 that protects against five childhood diseases.

Last month, Crucell month won a $30-million U.S. contract to develop vaccine to fight the Ebola and Marburg viruses.

HIV, the human immunodeficiency virus that causes AIDS, infects 2.7 million people each year, mostly in Africa.

Strong Immune Response

Barouch achieved the result by giving the monkeys two disabled cold-causing viruses six months apart. Each of these ``ferry'' viruses contained a hidden cargo: a single SIV protein that prompted the animals to produce masses of so-called ``killer T-cells'' that are primed to hunt and destroy SIV- infected cells.

A year after the first shots, the researchers gave the monkeys a lethal dose of SIV, and found their T-cells reduced SIV viral levels as much as 250-fold, stopping its spread and preventing the animals from progressing to simian-AIDS. Four of six monkeys who received placebo shots were dead by about 350 days.

``It certainly is better than the previous animal models, but we still don't know -- and it's a big if - whether this is going to translate into a meaningful and useful human model,'' Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, said in a Nov. 7 telephone interview.

Rare Virus Used

The vaccine may have worked because the researchers used a rare virus as the ferry for the first shot called adenovirus-26, to which humans don't typically have natural immunity. The ferry virus used for the second ``booster'' shot was the more common adenovirus-5, the same one used in the failed Merck trial, against which many people are immune.

Unlike Merck's monkey studies, Barouch and colleagues used only animals lacking a genetic mutation that predisposes them to fight SIV. That makes his results the ``most robust'' in years for adenovirus-based animal trials, Fauci said.

``He stacked the cards against himself,'' he said. ``It's another step in the direction hopefully that will get us to a T- cell based vaccine that would be of some use clinically.''

Barouch's team is now testing the adenovirus-26-based shot in a patient study at Brigham and Women's Hospital in Boston. They haven't yet decided which virus to use for the second shot, though it won't be adenovirus-5, and may be Ad26, Barouch said.

Both the monkey study and the ongoing human trial are funded by grants from the U.S. National Institutes of Health.

To contact the reporter on this story: Simeon Bennett in Singapore at sbennett9@bloomberg.net

Last Updated: November 9, 2008 13:00 EST

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