Mycobacterium tuberculosis DNA sequences encoding immunostimulatory peptides and methods for using same

Abstract

Nucleotide sequences isolated from Mycobacterium tuberculosis are disclosed. These sequences encode immunostimulatory peptides. Also disclosed are vaccine preparations formulated using these peptides.

Description

CROSS REFERENCE TO RELATED CASES[0001] This application is a continuation-in-part of co-pending U.S. application No. 08 / 990,823, filed Dec. 15, 1997, which is incorporated herein by reference. The 08 / 990,823 application claims priority from PCT application No. U.S. 96 / 10375, filed Jun. 14, 1996, which claims priority from U.S. Provisional application No.60 / 000,254, filed Jun. 15, 1995, all of which are incorporated herein by reference.I. BACKGROUND[0002] A. The Rise of Tuberculosis[0003] Over the past few years the editors of the Morbidity and Mortality Weekly Report have chronicled the unexpected rise in tuberculosis cases. It has been estimated that one billion people are infected with M. tuberculosis worldwide, with 7.5 million active cases of tuberculosis. Even in the United States, tuberculosis continues to be a major problem especially among the homeless, Native Americans, African-Americans, immigrants, and the elderly. HIV-infected individuals represent the newest group to be...

AI Technical Summary

Benefits of technology

[0020] The present invention also provides improved methods of performing the tuberculin skin test to diagnose exposure of an individual to M. tuberculosis. In this improved skin test, purified immunostimulatory peptides encoded by the nucleotide sequences of this invention are employed. Preferably, this skin test is performed with one set of the immunostimulatory peptides, while another set of the immunostimulatory peptides is used to formulate vaccine preparations. In this way, the tuberculin skin test will be useful in distinguishing between subjects infected with tuberculosis and subjects who have simply been vaccinated. In this manner, the present invention may overcome a serious limitation inherent in the present BCG vaccine / tuberculin skin test combination.

Problems solved by technology

Even in the United States, tuberculosis continues to be a major problem especially among the homeless, Native Americans, African-Americans, immigrants, and the elderly.

The emergence of multi-drug resistant strains of M. tuberculosis has complicated matters further and even raises the possibility of a new tuberculosis epidemic.

Resistant strains make treatment of tuberculosis extremely difficult: for example, infection with M. tuberculosis strains resistant to isoniazid and rifampin leads to mortality rates of approximately 90% among HIV-infected individuals.

While such an immune response normally clears infections by many facultative intracellular pathogens, such as Salmonella, Listeria, or Francisella, it is only able to contain the growth of other pathogens such as M. tuberculosis and Toxoplasma.

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