"This is the first recombinant tuberculosis vaccine to reach human trials in the United States," says NIAID Director Anthony S. Fauci, M.D. "Indeed, this is the first new TB vaccine to be tested in our country in more than 60 years. This candidate vaccine, as well as other novel products emerging from the TB research and development pipeline, offers hope for reducing the burden of a disease that claims approximately two million lives each year."
The vaccine combines two TB proteins known to stimulate strong immune responses in humans. The proteins were initially identified by screening blood taken from volunteers who never became ill with tuberculosis despite long-term infection with Mycobacterium tuberculosis bacteria. Using recombinant DNA technology, the TB proteins were fused and then combined with adjuvants, substances that further boost the immune system's response to the vaccine. NIAID grants awarded in the late 1990s supported research that uncovered the most effective adjuvant-protein combination.
NIAID's TB program officer, Christine Sizemore, Ph.D., notes, "This clinical trial is a wonderful example of advances made possible through sustained support and creative use of resources in NIAID's TB program." NIAID initially funded Corixa scientists, under the direction of Steven Reed, Ph.D., in their identification of the most promising TB proteins for use in a vaccine. Versions of the candidate vaccine were tested in animals through an NIAID contract facility at Colorado State University. In 2000, Corixa, with Dr. Reed as investigator, received an NIAID "challenge" grant designed to enhance government-industry partnerships and to speed new product development. This support allowed the researchers to further advance the most promising vaccine-adjuvant combinations into animal models, including non-human primates, and to prepare and produce a vaccine candidate suitable for human trials.
Finally, Dr. Reed and his team successfully competed for support through NIAID's Millennium Vaccine Initiative. This ongoing work is enabling the scientists to refine adjuvant technologies and to develop better methods of vaccine delivery.
The Phase I trial will enroll 20 volunteers at a single site in the United States and will assess the vaccine's safety. Researchers will examine blood from the volunteers to determine which dosage of vaccine promotes the greatest anti-TB immune response. If the vaccine proves safe in this initial stage of testing, it will be further tested for evidence of efficacy in larger clinical trials.
The currently available TB vaccine, called BCG, offers some protection against the form of TB most often contracted by very young children. But the vaccine's effectiveness wears off over time. Also, BCG is not very effective against pulmonary TB, the most contagious form of the disease.
NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
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