NIH 'blueprint' calls for $800 million commitment
NIH 'blueprint' calls for $800 million commitment
About 5% of annual U.S. TB control costs
The Blueprint for Tuberculosis Vaccine Development made its national debut recently when it was presented before an audience of TB experts gathered for a conference in San Francisco on the vaccine issue in late August. Developed by TB experts at the National Institutes for Health in Bethesda, MD, working with other national experts, the plan is now known as "the NIH blueprint."
Even though pouring more money into flagging TB control programs has worked to bring rising rates in the United States under control again, such an accomplishment can no longer be considered enough to eliminate TB, the blueprint says.
Nor is it certain that current declines will last, it adds. One factor that points toward the possibility that U.S. rates will rise again is the continued growth of the population, with the most projected for urban areas, the seed-beds of TB outbreaks. Other factors likely to boost TB rates include the AIDS epidemic; the global emergence of multidrug-resistant TB; and the globalization of the economy, which brings 49 million international travelers to the United States each year.
The authors also pointedly warn against reliance solely on current tools, including directly observed therapy (DOT). In the past, TB experts have mistakenly concluded that the various new discoveries - from streptomycin to Bacille Calmette-Guerin (BCG) to DOT - mean the struggle is over. What history shows is that only a vaccine which prevents the disease will solve the problem, the report says.
Acting locally means thinking globally
Problems with global spread of TB especially threaten to affect the United States, the report says, noting that "the failure to develop measures to prevent tuberculosis everywhere threatens our ability to control the disease anywhere, including the United States."
Globally, TB is a major killer, which imposes a huge economic burden, the blueprint says. The long-term commitment to develop a vaccine will thus require international collaboration and cooperation. Current tools are inadequate, given that BCG has shown only variable effectiveness, and that only 12% of TB cases worldwide are enrolled in programs which employ directly observed therapy, short-course, or DOTS.
The report notes that current research efforts have resulted in some striking accomplishments, including the sequencing of two strains of Mycobacterium tuberculosis. More than 100 candidate vaccines have emerged; and research continues on live attenuated vaccines, subunit vaccines, and naked DNA vaccines. An ideal candidate is defined as one that is safe, protects against both infection and disease, is long-lasting, and doesn't compromise the TB skin test.
The report lists three different kinds of Phase III trial designs for candidates which have been contemplated:
1. trials of pre-exposure vaccines designed to prevent either primary infection or establishment of latent infection;
2. post-exposure trials, which target those already infected;
3. total population trials of both types of effects.
Trials of post-infection vaccine candidates would require the enrollment of 6,000 to 24,000 subjects and would take 10 years of follow-up. Trials for pre-infection candidates would require 20,000 to 130,000 subjects, who would be followed for 20 years.
There are financial risks, the blueprint states, since the costs and payoffs are still unknown. Also unknown is whether any vaccine eventually discovered could perform as well as conventional vaccines. Though the effort to develop a vaccine will cost $800 million over 20 years' time, it is important to keep in mind that every year, the United States spends $700 million on control and treatment of TB.
Specific elements called for by the blueprint include:
r development of live animal models;
r basic research into the ways TB causes damage to the host, and into how the host protects itself;
r development of a diagnostic tool that can distinguish among those with active disease, those who are infected, and those previously vaccinated with BCG;
r development of pilot manufacturing facilities;
r establishment of repositories for samples from trials;
r identification of sources for reagents and supplies;
r evaluation of assays for trials.
Also proposed is the establishment of TB vaccine research units, or TVRUs, which would be charged with accomplishing many of the tasks listed above, and moving candidates through trials.
The NIH blueprint, which is still in draft form, is the culmination of a process that began when the Advisory Committee to Eliminate Tuberculosis, or ACET, wrote to U.S. Secretary of Health Donna Shalala, calling for a full-scale national commitment aimed at developing a new TB vaccine. Shalala's office responded by asking the committee to come up with a strategy for development.
As a result, the National Vaccine Program Office, which had also concluded there was an urgent need for a TB vaccine, teamed up with ACET, and the two entities approached the NIH for help in developing a strategy.
The three agencies convened a workshop on the subject in March last year. The blueprint, now in draft form and being circulated for comment, came out of that workshop.
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