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Merck Aids Vaccine Failure Signals Doom for African, U.S. HIV Vaccine Projects
  By John Lauerman
Jan. 31 (Bloomberg) -- The failure of Merck & Co.'s experimental AIDS vaccine may put an end to HIV prevention projects by the U.S. and GeoVax Labs Inc.
Merck halted a study, called STEP, in September after an unanticipated finding: people who got the vaccine were more likely to contract HIV than those who didn't. The result, to be discussed at an international AIDS meeting next week in Boston, has stalled human studies of similar vaccines, including one from the U.S. government that shares features with Merck's product.
The Merck vaccine was the most advanced of several preventatives against HIV, the AIDS-causing virus infecting more than 33 million people worldwide. Now, Anthony Fauci, the U.S. government's top infectious disease scientist, is waiting for more data from Merck and an international network of HIV researchers to determine whether the government's leading vaccine candidate, called VRC, will be safe enough to test.
``No final decision has been made on whether the trial is going to go forward,'' Fauci said in a telephone interview. ``If it does, it will probably be a modified, truncated version'' of earlier plans.
Scientists say the Merck fallout may set back vaccine research for years, and the other vaccines aren't as promising.
``There's a lot of disappointment,'' said John Bartlett, a Johns Hopkins University HIV researcher, in a telephone interview. ``Prevention is the biggest failure in the field, I think everyone agrees.''
Features in Common
The government vaccine contains a cold virus made by Gaithersburg, Maryland-based GenVec Inc. and a DNA vaccine made by San Diego-based Vical Inc. It has at least two features in common with Merck's. First, while most vaccines spur the body to make protective proteins called antibodies, the experimental AIDS shots stimulate protective T-cells, white cells the immune system uses to attack viruses.
Both vaccines also were built using the cold virus, called adenovirus-5. Proteins that can trigger a protective immune system reaction to HIV are packaged within the virus that delivers them throughout the body. Atlanta-based GeoVax is also testing a T-cell vaccine that contains a virus.
AIDS researchers are concerned because, in the Merck study, the people most likely to become infected with HIV were those who had high levels of immunity to the cold virus before the test began. If the U.S. trial goes ahead, it should probably enroll less than half the 8,000 or more people originally proposed, and exclude anyone with immunity to the cold virus, government science advisors said at a meeting in Potomac, Maryland, in December to discuss the vaccine's fate.
Eight Studies
Eight government-funded studies of vaccines against HIV, malaria and Ebola virus were halted or put on hold after the Merck results. The International AIDS Vaccine Initiative, based in New York, has stepped up efforts to find a way to prevent the disease that doesn't depend on triggering protective T-cells.
At the AIDS meeting next week, researchers are expected to give an in-depth analysis of data from the STEP study, which Merck and the HIV Vaccine Trials Network ran together. The data may tell Fauci whether the cold virus itself raised the risk of infection.
``What was the mechanism of why they had a greater incidence of infection and what's the relationship?'' he said ``It's going to be discussed, and it's going to be of great interest.''
At the December meeting of the government advisory group, the AIDS Vaccine Research Subcommittee, most researchers said they were in favor of going ahead with testing vaccines related to Merck's. The government's shot is sufficiently different from Merck's to be worth testing, said Gary Nabel, director of the Vaccine Research Center in Bethesda, Maryland, where the preventive was developed.
``We're not giving up, but we need to be intelligent about the approach,'' he said at the meeting. ``We need to move forward in a way that's constructive.''
Worth the Risk
Salim Abdool Karim, a vaccine researcher at the University of KwaZulu-Natal in South Africa, where the VRC may be tested, said the information to be gained in the test is worth the potential risk. A small trial would establish whether the vaccine is safe and provokes an immune response to HIV, he said.
``Given that we know so much about what this vaccine does in animals, it would be useful to see what it can do in people,'' he said in a telephone interview. ``I don't think the T-cell vaccines are dead because of this.''
Geovax's vaccine contains a virus called poxvirus. The product has significant differences from the Merck vaccine, and has given good results in animal tests, said Harriett Robinson, chief scientific officer and developer of the vaccine.
`T-Cells Important'
``You can't just say globally that T-cell vaccines won't protect against HIV,'' she said in a telephone interview. ``We know that T-cells are an important component of protection and they will continue to be.''
Geovax expects to enter the second of three phases of human testing of its vaccine in mid-2008. The three levels of testing are required for sale in the U.S.
Researchers from Whitehouse Station, New Jersey-based Merck may also have more information on whether other viruses made people in the vaccinated group more vulnerable to infection, said Michael Robertson, the company's director of HIV vaccines clinical research. For example, the herpes virus has been shown to increase the risk that people exposed to HIV will become infected.
``We think that work will be very interesting,'' he said at the Maryland meeting. ``We don't have anything that will shed any light on this so far.''
Phambili Trial
Researchers also want results from a second trial of the Merck vaccine that was under way in South Africa when the STEP results were released. The second trial, called Phambili, was stopped early, and patients who got the Merck vaccine were told they might be at higher risk of HIV infection.
The Phambili researchers had hoped to reveal at the Boston meeting, the Conference on Retroviruses and Opportunistic Infections, whether more vaccinated than unvaccinated people became infected. While the results won't be confirmed in time for the meeting, study leader Glenda Gray said she believes they will follow the same pattern as the STEP trial.
``We expect to see similar figures,'' said Gray, director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto, in a telephone interview. ``I think everyone would be surprised if it was different.''
To contact the reporter on this story: John Lauerman in Boston at .
Last Updated: January 31, 2008 00:14 EST
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