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September 27th, 2007, 07:31 GMT · By Stefan Anitei

The Struggle for Finding a HIV Vaccine

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It is the scourge of the 21st century and for over two decades scientists have been looking for an AIDS vaccine. But the long battle experienced a severe blow last week when a long-waited trial of a new HIV vaccine was prematurely stopped after failing in inducing any stop or slow down of the infection.

The STEP trial, funded by pharmaceutical giant Merck & Co. and HIV Vaccine Trials Network (HVTN), had come with the idea of boosting the immune killer T cells to kill for the virus more aggressively, by employing a weakened type of the cold virus carrying three HIV genes.

The vaccine was not expected to destroy HIV, but to hinder its growth, slowing down the development of full-blown AIDS and decrease a HIV infected patient's possibility of transmitting further the infection, as a temporary therapy
till the discovery of effective ones. Now, STEP has been discarded and hope comes from other 30 products in clinical testing.

"It was a very promising candidate. Getting this information, while it's disappointing, is really what this trial is designed to do, because [it] will move the field forward when we understand more about why [the vaccine] was not protective." said Susan Buchbinder, director of HIV research for the San Francisco Department of Public Health AIDS Office, and STEP protocol co-chair for the HVTN.

Vaccines usually work by stimulating the immune system to synthesize antibodies against a germ, but this type of approach does not work in the case of the rapidly mutating HIV.

The T cell approach was based on researches showing that such vaccines against SIV (simian immunodeficiency virus or monkey HIV) prolonged life and decreased infection in monkeys. STEP trials involved V520 virus with the three HIV genes (gag, pol and nef). Infected human cells by the experimental viruses produced the proteins encoded by these genes, offering T cells a previous exposure to them.

The STEP trial started in late 2004 and was made on 3,000 uninfected people in North and South America and Australia, who did not receive other vaccinations. A second trial of V520 was stopped in South Africa.

"Final results were set to be publicly released in 2008 or later, but an independent monitoring panel conducted a scheduled review of the vaccine's effectiveness and found that 24 of 741 participants injected with the vaccine had contracted HIV, compared with 21 of 762 given a dummy vaccine. The two infected groups had nearly the same levels of virus in the blood," stated Merck officials.

"This particular vaccine approach didn't work, but there are lots of different vaccine approaches in testing that produce different immune responses," said Buchbinder.

"The adenovirus used in V520 was altered so it couldn't reproduce, which may have limited its effectiveness. The next milestone will be later stage clinical testing of a vaccine developed by the federally funded National Institutes of Health Vaccine Research Center, which should begin next year. Also based on an adenovirus, it includes several versions of a fourth HIV gene-env." said Wayne Koff, senior vice president for research and development at the International AIDS Vaccine Initiative.

It seems that a single T cell-boosting vaccine is not enough to stop AIDS.

"Although disappointed in the results, the STEP trial results will likely give a shot in the arm to a growing effort to identify antibodies capable of neutralizing the virus before it causes a full-blown infection." said Koff.
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HIV
vaccine
gene

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