Product pipeline: Tuberculosis

Tuberculosis (TB) is a common and often deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. New infections occur at a rate of one per second. However, most of these cases will not develop the full-blown disease; asymptomatic, latent infection is most common. About one in ten of these latent infections will eventually progress to active disease, which, if left untreated, kills more than half of its victims. In 2004, mortality and morbidity statistics included 14.6 million chronic active cases, 8.9 million new cases, and 1.6 million deaths, mostly in developing countries.

Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully-susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low quality medication. Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs.

Since infection of cells with Mycobacterium tuberculosis leads to the expression of TB-specific latency antigens, a vaccine based on long peptides derived from these latency antigens will be highly specific for the infected cells. In a limited number of chronically infected individuals the infection eventually will lead to the induction of progressive (secondary) TB. An effective vaccine against TB latency antigens will therefore be highly valuable to protect infected individuals to the onset of TB disease as well as to prevent transmission.

In order to identify T cell epitopes in TB latency antigens, recombinant proteins and overlapping sets of synthetic peptides of ISA's proprietary latency antigens have been tested using cells from positive individuals. With the use of these results and of other assays, TB specific SLP's have been designed in order to obtain proof of immunogenicity with the designed TB long peptides in different mouse models.

ISA's next step in the development of the TB long peptide vaccine is to start clinical development.