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Uniting the fight against AIDS

AIDS experts say hunt for a preventive HIV vaccine will require systematic, worldwide collaboration between academic and industry partners
HIV Vaccine Trials Network colleagues Steven Wakefield and Banks Warden
HIV Vaccine Trials Network colleagues Steven Wakefield (left) and Banks Warden review possible sites for HIV vaccine-trial unit expansion in Brazil. Their study involves seeking locations where heterosexuals are at high risk for HIV infection. Photo by Todd McNaught

A vaccine to end the deadliest epidemic in history won't be found unless scientists unite in a global, coordinated research enterprise, say the world's leading AIDS experts.

In a paper published in the June 26 issue of Science, Dr. Larry Corey, principal investigator of the HIV Vaccine Trials Network (HVTN), Dr. Judith Wasserheit, the network's director, and 22 co-authors outline the need for a massive and integrated AIDS vaccine development effort-involving both academic and industry partners-that is strikingly different from the high-quality but separate research projects that exist today. Dr. Richard Klausner, executive director of the global-health program of the Bill and Melinda Gates Foundation and an affiliate investigator at the center, was lead author of the paper.

"We are now 20 years out from the identification of HIV of as the cause of AIDS," said Wasserheit, also an investigator in the Clinical Research Division. "We've spent hundreds of millions of research dollars and years of effort, yet we are still looking at a landscape in which only seven vaccine candidates were evaluated in humans in 2001 and 2002, with only one vaccine making it to large-scale human-efficacy trials.

"I think there is a very widespread feeling that the number of vaccine candidates making it into the pipeline is far from optimal."

About 3 million individuals died of AIDS and an estimated 5 million people acquired human immunodeficiency virus last year, bringing the global total of those infected to 42 million. Nearly 29 million already have died from the disease, and experts predict that if the epidemic proceeds at its current rate, there will be 45 million new infections by 2010 and nearly 70 million deaths by 2020.

"Our best hope, and the only long-term hope for preventing those predictions from becoming reality remains a vaccine," said Corey, a Clinical Research Division investigator and head of the center's Program in Infectious Diseases.

To accomplish this goal, he said, will require that scientists work together toward the greater good, an approach that is often at odds with the pressures felt by individual academic-research teams and biotechnology companies, whose funding or profitability depends on their ability to be the first to make a breakthrough discovery.

"If we are to succeed and develop true globally effective HIV vaccines, we need to change the structure that supports how vaccines are made, to coordinate factions and set aside intellectual-property parochialisms and other parochialisms," Corey said.

The frustrating pace of the vaccine effort spurred Corey and Wasserheit last fall to consider what it would take to establish a global vaccine hunt on the scale of the Human Genome or Manhattan projects. Together with Klausner and his Gates Foundation colleague Dr. Helene Gayle, they worked with a cohort of the world's most prominent AIDS experts to unite in a call to arms for a new vaccine-research enterprise that could overcome many of the current obstacles to success.

Chief among the logistical challenges have been the considerable overlap in vaccine development approaches among different research teams and the lack of participation by large pharmaceutical companies, which view drug development as a potentially more profitable and less risky venture than vaccine research.

"The number of companies that have taken on HIV vaccine development are limited and many of these are very small," Wasserheit said. "Even if a potentially effective candidate is developed, these companies aren't equipped to do the kind of mass production needed for large-scale human trials."

Vaccine-development centers

The authors suggest that a much more systematic, iterative approach by academic and industry partners is likely to yield the most success, as has been the case for medical achievements like the clinical trials that have led to dramatic cure rates in childhood leukemia. They propose mapping out possible research approaches for vaccine development onto a grid so that underrepresented areas can be identified and targeted and a roadmap can be created that defines which sectors need additional resources.

"Clearly, there is a major need to develop vaccines that elicit neutralizing antibodies to HIV," Corey said. "More effort and more work needs to be done to create novel vaccine products. To do this requires creating new structures for vaccine development."

The authors propose the creation of a set of six to 10 "HIV vaccine-development centers" devoted to this goal. The centers could be self-contained entities or virtual centers that represent novel collaborations among different institutions, with members that represent each aspect of the vaccine-development pipeline. Yet to be determined is how proprietary issues will be resolved within these collaborations.

Although organizational issues have impeded progress, Wassherheit said that the biological complexity of the AIDS virus has been the greatest stumbling block to vaccine development and demands the creation of new scientific-research consortia.

"All of the major obstacles spring from the scientific challenges," she said. "Among the greatest of these has been the inability to identify vaccine candidates that elicit an immune response that protects against the large diversity of circulating strains of the virus. We also still have a poor understanding of the mechanisms by which the immune system protects those individuals who have been heavily exposed to the virus yet don't exhibit signs of infection."

Despite what promises to be a hard road ahead as the proposed effort takes shape, Wasserheit said that a new collaborative spirit among research teams is already detectable.

"Our coming together to write the paper has stimulated new interactions, and there has been a dramatic increase in the level of communication among U.S. government players, such as the Centers for Disease Control, the National Institute of Allergy and Infectious Diseases and the Army," she said.

A meeting of the stakeholders will take place Aug. 20-21 in Washington, D.C. to discuss the next steps of moving to a blueprint of how the global enterprise will be implemented.

"Things are beginning to happen," Wasserheit said. "The proof will be in the pudding, but at this point, I think we've given the effort an important kick in the pants."

What is HVTN?

The mission of the HIV Vaccine Trials Network, established in 1999 by the National Institute of Allergy and Infectious Diseases, is to develop and test HIV preventive vaccines. The network is led by Clinical Research Division members Dr. Larry Corey, principal investigator, and Dr. Judith Wasserheit, director, and has more than 25 field sites on four continents.

Among the network's components is the Statistical and Data Management Center, located in the Public Health Sciences Division and directed by Dr. Steve Self. Fred Hutchinson, in conjunction with the University of Washington, also houses one of the network's clinical vaccine units and the lead facility for the HVTN's lab program, directed by Dr. Julie McElrath of the Clinical Research Division.

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