“We hope to have a vaccine ready for testing in about two years.” So said U.S. Health and Human Services Secretary Margaret Heckler about stopping the spread of HIV in 1984.

“It is no longer a question of whether we can develop an AIDS vaccine, it is simply a question of when.” So said President Clinton in 1997. His goal was to develop a vaccine to prevent HIV within 10 years.

According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), an HIV vaccine “could be available” by 2031. The world continues to wait.

While the road to a successful vaccine to prevent HIV may be lengthened by wrong turns and littered with obstacles, researchers insist they will find their way. They say a major breakthrough could happen at any point—if the world’s top minds share the same map.

To that end, two dozen scientific leaders in 2003 proposed creating a new organization to pool resources and harness the knowledge of researchers, funders and advocates working toward an HIV vaccine and help focus their efforts.

The result was the Global HIV Vaccine Enterprise, or the Enterprise, an independent organization that promotes collaboration and supports new approaches to addressing the challenges in HIV vaccine research.

Most of all, the Enterprise emphasizes sharing information and resources and working together to solve pre-identified challenges and reach clearly defined goals—instead of working in vacuums.

In 2004, all countries and governments in the Group of Eight (G-8) endorsed the Enterprise. In 2006, the Bill & Melinda Gates Foundation awarded the enterprise almost $300 million to establish vaccine development centers.

Alan Bernstein, PhD, executive director of the Enterprise, called the group a “meeting ground” where all the independent organizations working for a vaccine, such as UNAIDS and the National Institutes of Health, can come together.

Bernstein stressed that collaborating on one cohesive plan is what will advance the progress of vaccine work.

That plan, which is a blueprint for the work of alliance organizations, is called the Scientific Strategic Plan. First issued in 2005 and updated early in 2010, the plan has become a cornerstone of the Enterprise and serves as a guide. As Bernstein describes, the plan is the “glue and gravitational pull that gets us together.”

Developed by the Enterprise committee and molded from input from more than 400 researchers, policy makers, funders and advocates, the plan defines obstacles and opportunities, highlights areas that can benefit from increased cooperation and builds on the independent efforts and breakthroughs happening worldwide. It’s a plan of attack.

The 2010 plan identified two scientific priorities. First, the importance of HIV vaccine trials in people. Specifically, this entails integrating knowledge with product development, pushing for more trials, learning more from trials (extracting knowledge even when the trial is deemed a “failure”) and examining the creative ideas that emerge from trials, for example, in the realms of science and design.

“We learn so much from trials in people, not just how vaccines work, but something about what’s going on,” Bernstein said. “You don’t get to the top of the mountain with one step. The trials are the only vehicle to learn.”

And the second priority: the importance of preclinical models and making use of the advances made in biomedical sciences.

“We need to take advantage of all the latest sciences around HIV research, biology, physics, imaging,” Bernstein said. “We need to take advantage of things as quickly as possible.”

To achieve these goals, the plan outlines a number of steps. These include: exploring new trial designs; creating strategies to increase the number, efficiency and speed of trials; strengthening regulatory frameworks; ensuring trial data is compatible across specializations; expanding multidisciplinary HIV collaborations; and encouraging young scientists.

The plan also builds on lessons learned from past trials in preparing for the future.

In 2007, the field of HIV vaccine research suffered a morale-dealing blow when Merck Pharmaceuticals and the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health, stopped a promising clinical trial in progress. Not only was the vaccine found to be ineffective, but even more devastating, vaccines may have made some trial participants more receptive to HIV-1 infection, not less.  

But Bernstein says the “field is in a new era” partly because of technological advances and partly because of the “Thai trial.”

The trial Bernstein is referring to concluded in 2009 in Thailand and showed that an experimental vaccine could reduce the risk of HIV by more than 30 percent. While the results were modest and more research needs to be done, the trial made headlines.  

The AIDS Vaccine Advocacy Council called the Thai trial a “historic milestone,” and Colonel Jerome Kim, who helped lead the joint study conducted by the Thai Ministry of Health and the U.S. Army, said it was “the first evidence that we could have a safe and effective preventive vaccine.”

Scientists are also excited by new developments in the field of HIV antibodies, developments that can open avenues of research previously abandoned. According to John Mascola, MD, deputy director of the Vaccine Research Center at the NIAID, until now researchers believed that natural antibodies were rare and that perhaps it would be impossible to generate an HIV vaccine.

“However, recent discoveries have taught us that such antibodies are not nearly as rare as we thought,” Mascola said. “By studying how the natural immune system generates such potent antibody responses against HIV, we gain insights into vaccination strategies to do the same thing. If we could elicit such antibodies with a vaccine, prior to viral infection, high level protection against infection may be possible.”

But when will scientists be able to elicit those antibodies? That remains unanswered. The field of research can change dramatically overnight. While we are closer to developing and producing a successful vaccine, exactly how close we are is a mystery.

“The beauty of the scientific process is that we generally look back at what we knew 10 years ago and wonder how we got along with such limited knowledge and methods,” Mascola says. “It is safe to say that the next decade of research will bring unpredictable results, but I’m optimistic that these results will continue to demonstrate progress in vaccine efficacy.”

Those feelings were echoed by Bernstein.

“I’m optimistic about getting a vaccine, and I’m confident we’ll get there as quickly as possible,” Bernstein said. “But that’s as much a timeframe as I can give. Trials take time, and if it doesn’t work, you start all over again. And if it does, you have to scale up and give it to millions of people, and regulatory agencies take time. And so I hate to say this, but we need to be patient and impatient.”