Tuberculosis rv2386c protein, compositions and uses thereof

Abstract

The present invention is directed to a polypeptide which comprises: (i) an Rv2386c protein sequence; (ii) a variant of an Rv2386c protein sequence; of (iii) an immunogenic fragment of an Rv2386c protein sequence. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of tuberculosis.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. Ser. No. 13 / 055,787 which is the US National Stage of International Application No. PCT / EP2009 / 059585, filed 24 Jul. 2009, which claims benefit of the filing date of U.S. Provisional Application No. 61 / 083,699, filed 25 Jul. 2008, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to polypeptides and polynucleotides for use in the treatment or prevention of tuberculosis, in particular for use in the treatment or prevention of latent tuberculosis and in the prevention or delay of reactivation of tuberculosis (and also to related methods). The present invention further relates to pharmaceutical and immunogenic compositions comprising said polypeptides and polynucleotides, and to methods for the diagnosis of tuberculosis (in particular latent tuberculosis).BACKGROUND OF THE INVENTION[0003]Tuberculosis (TB) is a chronic infectious disea...

AI Technical Summary

Benefits of technology

The present invention relates to the identification of a new antigen called Rv2386c, which is associated with latent TB. The invention provides a polypeptide that includes the Rv2386c protein sequence or a variant of it, as well as an immunogenic fragment of it. The polypeptide or a nucleic acid sequence encoding it can be used as a medicament to treat or prevent TB, particularly latent TB and the reactivation of TB. The invention also provides a method for inducing an immune response against Rv2386c to prevent or delay TB. The use of Rv2386c or a combination of it with other antigens can also enhance the immune response to TB.

Problems solved by technology

It is a major disease in developing countries, as well as an increasing problem in developed areas of the world.

Although an infection may be asymptomatic for a considerable period of time, the active disease is most commonly manifested as an acute inflammation of the lungs, resulting in tiredness, weight loss, fever and a persistent cough.

If untreated, serious complications and death typically result.

Tuberculosis can generally be controlled using extended antibiotic therapy, although such treatment is not sufficient to prevent the spread of the disease.

Infected individuals may be asymptomatic, but contagious, for some time.

In addition, although compliance with the treatment regimen is critical, patient behaviour is difficult to monitor.

Some patients do not complete the course of treatment, which can lead to ineffective treatment and the development of drug resistance.

Sensitivity and specificity have, however, been a problem with this test, and individuals vaccinated with BCG cannot always be easily distinguished from infected individuals (this is particularly important in light of the fact that BCG does not protect against latent infection).

However, this rule is not applicable to individuals with immunosuppression due to HIV infection, which may result in a PPD reaction below 10 mm in diameter); or in endemic countries, where people infected by non-tuberculosis mycobacteria can show a PPD reaction above 10 mm in diameter.

However, since ESAT-6 / CFP-10 are early stage antigens, assays based on ESAT-6 / CFP-10 may only perform optimally in recently infected people.

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