By Marc Kaufman
Washington Post Staff Writer
Friday, June 27, 2003; 3:53 PM

Declaring that the two-decade search for a vaccine against HIV-AIDS has fallen disturbingly short of its goals, the world's leading researchers in the field called yesterday for an international effort on the level of the Human Genome Project to speed a breakthrough.

Writing in the journal Science, two dozen HIV-AIDS leadersurged creation of a Global Vaccine Enterprise that would establish six to 10 new research centers around the world focused exclusively on an AIDS vaccine, funded by new public and private money.

"Almost everyone involved in HIV vaccine development agrees that there is an urgent need to create and evaluate systematically more candidate vaccines," wrote the AIDS elite, including top U.S. and international public health officials, two Nobel Prize winners, corporate and foundation researchers, and activists representing AIDS sufferers. "Despite the wide variety of conceptual approaches to HIV vaccine design, the pace of development of new HIV vaccine candidates needs to be accelerated."

One of the paper's authors, Seth Berkley, president of the International AIDS Vaccine Initiative, was more direct in an interview.

"It's more than 20 years since AIDS was diagnosed, and the amount of money spent for a vaccine has been a global disgrace," he said. "Yes, the science is very difficult. But unless the world really pushes for an AIDS vaccine, we'll never know what is possible and what is not."

The call for a major new approach to developing a vaccine comes after years of minor successes and major disappointments in the lab and in clinical trials. In the past two years, only seven possible candidates for a vaccine have gone into human trials, and only one entered phase III clinical testing for effectiveness. In February, that once-promising effort-15 years in development-failed to show significantly protective results among the more than 5,000 men and women who took it.

It has been especially difficult to develop an AIDS vaccine, because the virus mutates so quickly and because existing methods of stimulating the immune system to make antibodies to kill the virus have proven ineffective.

According to co-author Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, none of the 60 million people who has contracted the virus has recovered on his own, leading scientists to conclude that the body cannot produce effective antibodies against it. Virtually all vaccines work by introducing elements of a microbe or toxin into the body to cause it to produce antibodies that protect against later infection.

According to the paper, about 45 million people will be infected with the virus by 2010, with nearly 70 million deaths by 2020. Most of the victims now are in poorer countries in Africa and Asia.

Berkley said that only 2 percent of global funds spent on HIV-AIDS goes to developing a vaccine, which is the only way the epidemic can be stopped. "Let's face it: Once the demand for treatment grew and billions began flowing into that, the AIDS vaccine has fallen way down the agenda," he said.

But the vaccine effort has been limited because large drug companies, with the exception of Merck & Co. and Aventis Pasteur, have not been particularly active in the field. Another author, Peter Piot, executive director of the Joint United Nations Programme on HIV-AIDS, said their absence "has to be seen as a major market failure."

In calling for the creation of a global network of centers to work on an AIDS vaccine, the paper's authors said they will need help not only to discover a vaccine, but also to test and manufacture it.

Co-author Lawrence Corey, of the HIV Vaccine Trials Network at the Fred Hutchinson Cancer Research Center at the University of Washington, said one significant problem facing AIDS vaccine researchers is that, because of a worldwide shortage of manufacturing capacity, many months often pass before a potential vaccine can be produced

He said some authors contended that a manufacturing facility should be built as part of a renewed global effort; others proposed paying for dedicated time on the production lines of drug makers.

Corey also said the global approach to an AIDS vaccine has generally been to "hope that someone hits a grand slam. But we're saying here that we're more likely to have success by a process of small advances and the creation of vaccines that can help some people, but not all."

The lead author on the paper is Richard Klausner, executive director of global health for the Bill & Melinda Gates Foundation, which has funded some of the largest AIDS vaccine projects around the world. He said private organizations and governments must accept most of the burden in the AIDS vaccine effort, and that the Gates Foundation is willing to contribute more.

"Recent progress has actually shown us how hard this problem is going to be," Klausner said in an interview. "Considering how great the challenges are, I think it's going to be very difficult without the type of international structure and effort we've outlined."

He said the authors will break into expanded working groups to develop a "road map" for jump-starting and focusing the global enterprise. He said the model of the Human Genome Project-in which individual labs were spurred to work faster and more closely together -- was appealing to the group.

In pressing for six to 10 AIDS vaccine centers around the world, the paper looked to the Vaccine Research Center of the National Institutes of Health as a model. The authors did not try to estimate the cost of a global effort, but Fauci said the U.S. program has a fiscal 2004 budget of $456 million, making it the leading force internationally in AIDS vaccine research.

"Others are doing some significant work, and there are some who we think should be doing more," he said. "What we're trying to do in this paper is really catalyze the idea that we need a global enterprise for an AIDS vaccine."

Among the co-authors on the paper were Nobel Prize-winning biologist David Baltimore, president of the California Institute of Technology; Nobel Prize winner Harold Varmus, a former NIH director who is president of Memorial Sloan-Kettering Cancer Center; Julie L. Gerberding, director of the federal Centers for Disease Control and Prevention; Donald P. Francis, president of VaxGen Inc.; and researchers from France, England, India, South Africa and China.