BioWorld Today Correspondent

BOSTON - The prospect of a vaccine against AIDS is no closer than when the HIV virus was uncovered as its infectious source in the early 1980s.

This is the pessimistic assessment of the world-leading authority in the disease, David Baltimore, in his presidential address to the American Association for the Advancement of Science meeting. "There is no AIDS vaccine and no hopeful candidate vaccine," he said.

He added that the issue is "such a sad topic." In 1986 when he reviewed the field, he suggested a vaccine was at least 10 years away. "You are quite within bounds to ask; If it has been 10 years away for the past 20 years, will it ever happen?"

While there are people who say it is impossible to develop a vaccine, Baltimore himself wants to remain optimistic. Though he gives a pretty dismal assessment of the prospects, he said, "It is too important: there ought to be a way," and he called on the U.S.'s "prowess in biotechnology" to try and find an effective vaccine.

The reason Baltimore believes the cause is so hopeless is that the HIV virus that sparks AIDS has evolved to be virtually impossible to attack with antibodies. Without antibody sensitivity it is pretty well uncontrollable by the immune system.

"This is a huge challenge because to control HIV immunologically the scientific community has to beat out nature, do something that nature, with its advantage of 4 billion years of evolution, has not been able to do."

After trying and failing to control HIV through antibodies, the next approach was to use the other arm of immune protection, the cellular immune system. Baltimore said it was "a jolt" last year when Merck and Co Inc.'s vaccine failed in the first full-scale clinical trial of such a vaccine.

The failed vaccine, V520, consists of a genetically modified adenovirus loaded with three synthetic HIV genes. The Phase II trial testing the product in volunteers at high risk of acquiring HIV was stopped in September 2007 by the data safety monitoring board.

"I was hopeful we would see a glimmer of efficacy; in fact, we saw a glimmer of the reverse," Baltimore said. Although not statistically valid, there was some evidence of an increase in infections in subjects who received the vaccine vs. placebo.

"The [vaccine] community is depressed because we see no hopeful route to success," he said, adding, "I should add that this depression is not halting development activities. Knowing how crucial it is to get a vaccine, developers are moving ahead, even recognizing the long odds for success."

While some researchers continue to work on antibody approaches, others are trying to improve on cellular immune system vaccines by increasing T-cell coverage and improving delivery. Depressingly, Baltimore said such attempts offer the prospect of "incremental improvements on zero."

Baltimore himself is working on a whole new approach. "I don't want to pretend we have found the route. We are looking at a combination of gene therapy, immunology and stem cell therapy, all of which are trendy and difficult."

The concept is to use a vector to deliver T-cell receptor genes and antibody genes to change haematopoietic stems cells and generate an immune response. The genes themselves will not be naturally occurring. "We are saying to our structural biology friends, 'Design the best anti-HIV molecule, and then we will try and make humans able to express that protein,'" he noted.

Initially, it is hoped that will work as a therapeutic. Baltimore has funding from the Bill and Melinda Gates Foundation Grand Challenges program and is now two and half years into the project.

"I can report that it is as difficult as we imagined," he concluded. "We are still in the stage of delivering the tools, the systems and the materials we need to even attempt a serious test of the idea."