Tuberculosis

Pulmonary macrophages are the principal host of tuberculosis, where it can remain latent and inaccessible to current TB drug therapies. Dmitry Shayakhmetov of the University of Washington will study whether infecting these host cells with adenovirus will induce rapid cell death, reducing TB load and blocking the re-infection cycle.

Matyas Sandor of the University of Wisconsin will graft granulomas, nodules that form as a result of long-term inflammation, to study the role they play in TB latency and reactivation.

Sarah Fortune of Harvard University will research whether chromatin crystallization, in which DNA condenses into a protective matrix due to environmental stress, occurs in tuberculosis and is a characteristic of latent organisms.

Axel Heiser of AgResearch Ltd. in New Zealand proposes to develop a new type of tuberculosis vaccine that uses polyester biobeads produced in mycobacteria that carry a large repertoire of known and undiscovered antigens on their surface. This new technology combines the multiple antigenic benefits of live vaccines with a better safety profile and lower costs of production.

Jennifer Andrew of the University of Florida in the U.S. will develop a non-invasive diagnostic platform for the detection of tuberculosis (TB). Nanoparticles will be attached to a polymer matrix to form a dry powder for delivery by inhalation to the lungs, where the presence of TB-infected cells will stimulate nanoparticle release. A simple test strip will detect the presence of released nanoparticles in urine within four hours as a rapid field-based TB diagnostic.

Arturo Casadevall of Albert Einstein College of Medicine in the U.S. will work to develop a new vaccine for tuberculosis that uses an arabinomannan-protein conjugate to elicit strong antibody-mediated immunity. M. tuberculosis has a polysaccharide capsule composed of arabinomannan, which, when used as part of a vaccine, could lead to an immune response that prevents inflammation and disease transmission without impairing clearance of the bacteria.

Anthony Baughn of the University of Minnesota in the U.S. will test a library of cyclic peptides to identify small molecules that impair the ability of the tuberculosis- causing bacterium M. tuberculosis to develop resistance to current drug therapies, for use in a new class of tuberculosis antibiotics.

Paul de Figueiredo and colleagues at Texas A&M University in the U.S. propose to develop a system whereby drugs for defeating new antibiotic-resistant strains of Mycobacterium tuberculosis can be developed in the laboratory before these strains emerge in human populations.

Christopher Vinnard of Drexel University in the U.S. proposes to develop a low-cost point-of-care urine test that can safely and accurately identify tuberculosis patients who poorly absorb anti-TB drugs. Testing patients for inadequate drug bioavailability could enable better drug dose optimization and decrease transmission rates.

Pavan Muttil of the University of New Mexico in the U.S. will test the theory that inhaled live BCG immunization will elicit a stronger and more sustained immune response in mammals that have been exposed to mycobacteria than conventional intradermal BCG immunization. The new administration method could overcome the present variable protection to tuberculosis offered by the current intradermal technique.