Novel compositions and methods

Inactive Publication Date: 2011-05-19
GLAXOSMITHKLINE BIOLOGICALS SA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0061](ii) administering to said subject a safe and effective amount of a polypeptide or polynucleotid

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 tr

Method used

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  • Novel compositions and methods
  • Novel compositions and methods
  • Novel compositions and methods

Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification of Rv3616c as a latent TB Vaccine Target

[0574]The gene Rv3616c encodes for a conserved hypothetical alanine and glycine rich protein. Rv3616c was selected based on a genome-wide analysis of Mycobacterium tuberculosis genes associated with dormancy phase maintenance and infectivity as in Murphy and Brown BMC. Infect. Dis. 2007 7:84-99. Potential dormancy phase gene targets in Mycobacterium tuberculosis were prioritised through a bioinformatics meta-analysis of published genome-wide DNA microarray datasets of bacterial gene expression under simulated dormancy conditions. Subcellular localisation of M. tuberculosis proteins encoded by genes, was subsequently carried out on the entire genome to identify vaccine targets.

[0575]Briefly, experimental conditions in the dormancy models were quite varied so a zero to five scoring system was developed to normalise these data based upon two criteria: 1) the relevance of the experimental conditions to the dormant state and 2) the r...

example 2

Rv3616c Epitope Prediction

Method

[0586]T cell epitope prediction was based on the following approaches:

PredictionNameURL / ReferencesCD4 andMultipredwebsite: antigen.i2r.a-star.edu.sg / multipred / CD8Zhang, G. L., Khan, A. M., Srinivasan, K. N., August, J. T. andBrusic, V. (2005) “MULTIPRE d: a computational system forprediction of promiscuous HLA binding peptides” Nucleic AcidsRes. 33, W172-W179.SVMHCwebsite: www-bs.informatik.uni-tuebingen.de / SVMHC“Prediction of MHC class I binding peptides, using SVMHC.”Pierre Donnes and Arne Elofsson in: BMC Bioinformatics 20023: 25CD4ProPredwebsite: www.imtech.res.in / raghava / propred / Singh, H. and Raghava, G. P. S.(2001) “ProPred: Prediction ofHLA-DR binding sites.” Bioinformatics, 17(12), 1236-37.Tepitope2In house program based on:H. Bian, J. Hammer (2004) “Discovery of promiscuous HLA-II-restricted T cell epitopes with TEPITOPE.” Methods 34: 468-75CD8nHLAwebsite: www.imtech.res.in / raghava / nhlapred / Bhasin M. and Raghava G P S (2006) “A hybrid approac...

example 3

Rv3616c Epitope Identification

[0589]A range of 30 overlapping peptides covering the full length of Rv3616c were prepared (see FIG. 1 for details and SEQ ID Nos: 127-156) and tested for their ability to stimulate PBMC from four PPD+ donors.

[0590]The data, shown in FIG. 2, reveals that peptides 1-7 and 17-30 were immunogenic for these individuals.

[0591]It should be noted that peptides 8-16 (amino acid residues 92-215) may be immunogenic in other individuals of differing HLA type.

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Abstract

The present invention is directed to a polypeptide which comprises: (i) an Rv3616c protein sequence; (ii) a variant of an Rv3616c protein sequence; or (iii) an immunogenic fragment of an Rv3616c protein sequence for use in the treatment or prevention of latent TB. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of latent tuberculosis.

Description

FIELD OF THE INVENTION[0001]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[0002]Tuberculosis (TB) is a chronic infectious disease caused by infection with Mycobacterium tuberculosis and other Mycobacterium species. It is a major disease in developing countries, as well as an increasing problem in developed areas of the world. More than 2 billion people are believed to be infected with TB bacilli, with about 9.2 million new cases of TB and 1.7 million deaths each year. 10% of those infected with TB b...

Claims

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Application Information

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IPC IPC(8): A61K39/04A61P31/06
CPCC07K14/35A61K39/04A61P31/06A61P37/04A61K49/00
Inventor METTENS, PASCALBROWN, JAMESMURPHY, DENNIS
Owner GLAXOSMITHKLINE BIOLOGICALS SA
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