In an effort to control the alarming spread of tuberculosis (TB) across the globe, a team of researchers has created a strategic plan or "blueprint" that sets guidelines for developing an effective TB vaccine. Vaccination is the only line of attack that will conquer the disease, which kills an estimated 1.5 to 3 million people around the world each year, more than any other single infectious disease. The "Blueprint for TB Vaccine Development" identifies the TB crisis as a global health priority and encourages an international collaborative effort to develop a vaccine. The "Blueprint" appears in a special TB supplement to the "Clinical Infectious Diseases" journal.

"The development of a TB vaccine requires long-term commitment and collaboration by governments, TB control programs, scientists, industry and academia, both nationally and internationally," says Ann Ginsberg, M.D., Ph.D., tuberculosis and leprosy program officer at the National Institute of Allergy and Infectious Diseases (NIAID) and a co-author of the report.

The "Blueprint" was developed at a TB workshop held in March 1998 by NIAID and the National Vaccine Program Office. A taskforce convened by the Department of Health and Human Services now oversees the implementation of the plan.

"The 'Blueprint' serves as a call-to-action and rough battle plan for the development of a TB vaccine, and demonstrates that a coherent plan is in place and being followed as current resources allow," says Dr. Ginsberg, who represents the NIH on the taskforce.

According to the "Blueprint," 54 million people become infected worldwide with TB each year. The only currently available TB vaccine, called BCG, is largely ineffective and interferes with skin tests used to diagnose the disease. As a result, BCG vaccine is not recommended for use in the United States. However, BCG is effective against early childhood tuberculosis and is recommended by the World Health Organization as part of an immunization schedule for infants in countries where the disease is rampant.

An ideal vaccine would be safe, long-lasting, inexpensive, not interfere with skin tests used for diagnosis, protect against development of disease and possibly even block infection.

Development of a TB vaccine presents a significant challenge. TB bacteria replicate very slowly, making them difficult to study. And because TB is highly infectious and dangerous to work with, scientists must use appropriate safety standards and equipment when working with the bacteria in vaccine development.

The report details three different vaccine concepts currently being developed: live, attenuated vaccines; subunit vaccines; and naked DNA vaccines. In one live, attenuated vaccine approach, scientists genetically modify the TB bacterium in the laboratory, thereby reducing its ability to cause disease. When inoculated into humans, the weakened bacteria should induce an immune response but not cause disease. In the subunit vaccine approach, scientists dissect the TB bacterium and use only a fragment of it in the vaccine to produce an immune response. In naked DNA vaccines, a relatively new vaccine strategy, scientists take DNA from the TB bacterium and modify it so only a small piece of the original genetic material is left. This modified, naked DNA when inoculated into humans prompts the body's own cells to generate protective immune responses against the disease.

Once scientists have identified a promising vaccine candidate, they will study its safety and effectiveness in human clinical trials.

Information On TB

TB is a contagious disease spread through the air when a person with active TB expels "M. tuberculosis", the bacterium that causes TB, by coughing, sneezing, speaking or laughing. Once inhaled, the bacteria travel to the lungs and attach to air sacs, known as alveoli, where they multiply. The bacteria may cause active disease, or they may persist at a low level for years before causing disease, a condition known as latent infection. Currently, 10 to 15 million people in the United States have latent infection, and 10 percent of them will develop active disease at some point in their lives.

TB infection is particularly deadly for people with weakened immune systems, such as individuals already battling HIV infection. An HIV-positive person is up to 30 times more likely to develop TB disease, which in turn accelerates HIV disease. TB is the leading cause of death in HIV-positive people.

Current TB drug regimens require long treatment periods, and many patients stop taking the drugs as soon as they start feeling better, which can lead to the emergence of drug- resistant strains. Population growth, inadequate public health infrastructure, globalization and international travel, the growing HIV/AIDS epidemic, and the emergence of multi-drug resistant TB strains (strains that are resistant to two or more of the most commonly used drugs to treat TB) all contribute to the growing global TB epidemic.

NIAID supports a comprehensive TB research program and follows the "Blueprint" guidelines in conducting vaccine research and other anti-TB treatment studies. The "Blueprint" is available on the NIAID Web site at www.niaid.nih.gov/publications/blueprint For more information on TB and vaccine research, please visit the NIAID publications page at http://www.niaid.nih.gov/publications/.