Successes, failures mark 30 years of HIV/AIDS research

It is difficult to put your finger on why, almost exactly three decades after the first case of AIDS was reported, there is now a general feeling in the scientific community that big breakthroughs are coming soon in AIDS vaccines, treatments and prevention. It is not only that big financiers like the Bill & Melinda Gates Foundation are contributing millions to the eradication of HIV (although that certainly helps). It's that the 30 years spent on understanding the virus that causes AIDS is at last making sense in a coherent way.

Breakthroughs in genetics, drug delivery, vaccines, computer modeling and other disparate disciplines are all converging onto their target. Even recent vaccine failures have opened up new avenues of inquiry.

"This is a pivotal moment in HIV vaccine research," Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, recently told Reuters. "The last five years have been the richest period in HIV vaccine research since the epidemic began. The question...now is how do we build on these scientific advances?" He added that cross-border and cross-discipline collaboration among scientists was crucial.

Much work still needs to be done to rid the world of this modern-day plague that has cost so many lives, but it seems to be with renewed focus, AIDS research is moving forward. With antiretroviral combination drugs as treatment and possibly prevention, and a reinvigorated vaccine search, it is possible that HIV/AIDS could eventually go the way of smallpox into the dustbin of history.

Vaccines

'Mosaic'

HIV, the virus that causes AIDS, has a frustrating ability to evolve rapidly. Think of all those science-fiction movies where some sort of out-of-control machine intelligence seems to be defeated at first, then comes back stronger as it adapts to the weapons used against it. That is what HIV does, and how it frustrates and foils those who think they have found a single weapon to use against it.

The answer, then, is that there is no single ultimate weapon that can be used against HIV. And that is where current vaccine research is taking us. The next generation of HIV vaccines are known as "mosaics." They are composed of many sets of synthetic, computer-generated sequences of proteins that can prompt the immune system to respond to a variety of strains. Such vaccines have shown success in animal studies, and new trials will test the mosaic concept and could possibly lead to the next generation of HIV vaccine candidates.

A new consortium, funded in part by the Bill & Melinda Gates Foundation, is trying for a Mosaic vaccine, hoping to launch trials by late 2012.

Thai trial

The one vaccine trial that just about everybody who follows HIV developments references as a success is commonly known as the "Thai Trial." It was a vaccine trial in Thailand known as RV 144 that began in 2003 and ended in 2006, with results released in 2009. Those who received the vaccine saw a 31 percent drop in HIV infection compared to those who received placebo, prompting many to declare RV 144 the first vaccine to give any supporting evidence of having lowered the risk of contracting HIV.

The prime vaccine was ALVAC‐HIV, which consisted of a viral vector of genetically engineered versions of three HIV genes (env, gag and pro). It is manufactured by Sanofi Pasteur. The booster vaccine was manufactured by Genentech under a license and supply agreement with VaxGen.

The approach the trial took is known as "prime boost," which is essentially administration of one type of vaccine followed by a second type. The idea is to enhance the body's immune responses to the virus.

The Thai trial is being studied closely as the model for future development of a final vaccine.

Crucell

Building on the encouraging results of the Thai trial, Crucell is joining with a host of collaborators to develop a prime-boost combination vaccine. Working with researchers from Harvard University's Beth Israel Deaconess Medical School and the Ragon Institute, the Dutch biotech plans to mix its vaccine with a candidate from the International AIDS Vaccine Initiative in the prime-boost approach. The investigators will track the combination vaccine's safety as well as its ability to provoke an immune response among healthy volunteers.

If the Phase I trial is successful Crucell says they can pursue plans to mount a proof-of-concept Phase IIb study. The research work is supported by the National Institute of Allergy and Infectious Diseases. It might have been Crucell's work on the AIDS vaccine that convinced Johnson & Johnson that it wanted to buy Crucell, in part to boost its own vaccine program. Next page >>

Successes, failures mark 30 years of HIV/AIDS research
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