Surgeon general endorses blueprint for TB vaccine

Cooperation critical to accelerate vaccine search

U.S. Surgeon General David Satcher, MD, gave a thumbs-up to the 20-year long-range plan, or "blueprint," which maps out the strategy for developing a better vaccine against tuberculosis. At a December 16 meeting in Washington, DC, in which he was briefed on the blueprint, Satcher expressed his commitment to seeing the plan through to implementation, says Anthony Fauci, MD, chief of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, MD. "He’s definitely heavily invested," Fauci says.

Present at the meeting were top-level representatives from the National Institutes of Health (NIH), the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the United States Agency for International Development, and the U.S. Advisory Committee for Elimination of Tuberculosis (ACET).

In addition to being surgeon general and assistant to U.S. Secretary of Health Donna Shalala, Satcher directs the national vaccine program. Gaining his approval was a critical step in the process of securing the estimated $800 million in funds that will be needed to implement the strategy outlined in the blueprint, says Dan Salmon, MPH, policy fellow at the Atlanta-based National Vaccine Program Office (NVPO).

Goal: Establish framework of cooperation

Money, however, wasn’t the primary focus of the briefing, Fauci says. Instead, talk focused on concepts presented in the blueprint. "The subject of funding came up only once or twice; but obviously, some new money will be needed. What we’re trying to do right now is establish a framework for the next 10 to 20 years so we can make sure that we have the necessary resources."

Satcher told the group its next task is to put together an interagency task force, which will be charged with implementing the strategies outlined in the blueprint. "The task force’s first job will be to attach a budget to the plan of action," says Ann Ginsberg, MD, PhD, program officer for tuberculosis, leprosy, and other mycobacterial diseases in the Division of Microbiology and Infectious Dis eases at the NIH in Bethesda, MD. "Second, they will be charged with overseeing all the activities related to vaccine development, making sure all the players are talking to each other and coordinating their work."

Satcher made a point of complimenting the group on its work. "He said it was gratifying to see so many agencies and departments coming together with such a well-coordinated plan and presenting such a good briefing, and that it was clear everyone had worked really hard on this," says Salmon. "It was a nice pat on the back."

According to blueprint estimates, it will take about $800 million over the next 20 years to develop a vaccine against TB that works better than BCG. Some of that money will come from in-house sources such as the CDC and NIH, Fauci says, but the rest presumably will be new money that will have to be appropriated by Congress on an annual basis.

Already, the NIH has elevated the development of a TB vaccine to a top priority with budget decisions reflecting that change, Fauci says. "In 1991, my institute’s budget for TB was $3.7 million," he says. "In 1999, it’s $41.5 million. So as you can see, we’ve greatly accelerated our TB budget. A lot of that [money] will ultimately feed into what we need for the development of a vaccine."

Though the strategic plan has become known as "the NIH blueprint," Fauci and others at the meeting with Satcher emphasize it by no means represents the NIH alone. "It’s an interdepartmental blueprint; the NIH is just one of many players," Fauci says.

During the meeting with Satcher, Fauci outlined what the NIH sees as its roles:

• continue conducting vaccine research;

• explore new avenues of research expected to spin off from the completion of the sequencing of the TB genome;

• help develop an international network for conducting Phase I, II, and II trials for testing candidate vaccines developed in the laboratory.

The creation of the vaccine blueprint reflects a growing sense in the public health community, both in the United States and abroad, that the fight to eliminate TB cannot be won without a better vaccine. That conclusion has led TB researchers not just to look for more funding for their efforts, but also to better coordinate those efforts.

"If you were to throw a billion dollars at [vaccine development], but efforts weren’t well-coordinated, the money would probably have limited utility," Salmon points out. "Likewise, if you had a great plan but no resources, you wouldn’t get much accomplished, either."

Increase private-sector involvement

Although its members haven’t been determined, creation of the task force already is proceeding in high gear, says Salmon. "We’ve decided it’s of utmost importance to move very quickly on this."

The hope is that better coordination will move research forward at a faster pace, with more attention paid to some key areas that have been lagging behind, says Ginsberg.

In the short-term, the blueprint aims to increase private-sector involvement, involve vaccine manufacturers at an earlier stage in research occurring in public and academic circles, and better coordinate the work of the private sector with the other two spheres of endeavor, she says. "There’s a fair amount of interest among vaccine-makers, but they’ve been holding back, waiting for proof of principle. If any of the candidate vaccines looked consistently better than BCG in the animal models, manufacturers would begin to gear up and hop on board."

The fact that BCG is still used as the gold standard points to another gap that needs to be addressed, she adds. BCG is used as the standard because it gives such good protection against TB in animal models; but in humans, clearly, it works far less effectively.

"One thing that’s telling us is that our animal models aren’t good enough yet," Ginsberg says. "A lot more work needs to be done on finding a better animal model."

Originally, the blueprint was developed from a workshop the NIH held in conjunction with the NVPO last March. Since then, its authors have gotten "a lot of input from the broad research community as well as from the vaccine-development community," she adds.

Last August, the blueprint was presented to an international symposium, and copies have been circulated among industry and academic leaders. This past fall, a revised blueprint was approved by ACET and the National Vaccine Advisory Committee.

A higher profile for vaccine development

"Ultimately, what we hope the blueprint will do is produce a new vaccine within the next 20 years," says Ginsberg. "But in the shorter term, we hope it will raise the profile of TB vaccine development as a priority, both here and globally. We need to get all the various players more involved, including the funding agencies, the academic scientists, the vaccine manufacturers, and all the other stakeholders."

That effort will require both better coordination and more funding, she adds. "More money, yes; it’s clearly going to take more money than is currently being devoted. But we also need to coordinate and get all the partners involved as early as possible."

Satcher, appointed to the post of surgeon general last February, has devoted a big part of his career to championing the fight against infectious diseases, and he has warned repeatedly against complacency in that struggle. As a 2-year-old boy growing up in Anniston, AL, he nearly died of whooping cough; that experience spurred him, while head of the CDC, to lead a nationwide drive to increase childhood vaccinations. He began his practice as a family physician working in inner-city health clinics and urban hospitals, and he regards the poor as his most important constituents.

When he was nominated to the post of surgeon general, Satcher said his goal was "to make the greatest difference to those who have the greatest need."