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
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
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/.
A Ginsberg. A proposed national strategy for tuberculosis vaccine development. "Clinical Infectious Diseases" 30(suppl 3):S233-42 (2000).