Health Protection Agency

Secretary of State for Health and Social Care

Philip Marsh

Brian William James

Joanna Bacon

Tobias Hampshire

Yper Hall

The present invention provides an antigenic composition for use as a mycobacterial vaccine, said composition comprising (i) a first mycobacterial antigenic polypeptide, wherein said first mycobacterial antigenic polypeptide comprises a polypeptide sequence having at least 70% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 6, 12, 2, 18, 8, 10, 16, 4, or a fragment thereof having at least 50 consecutive amino acids thereof; or (ii) a first mycobacterial polynucleotide, wherein said first mycobacterial polynucleotide comprises a polynucleotide sequence encoding said first mycobacterial antigenic polypeptide, or wherein said first mycobacterial polynucleotide comprises a polynucleotide sequence selected from SEQ ID NO: 5, 11, 1, 17, 7, 9, 15, 3.

Mycobacterial antigen composition

A method is provided for identifying mycobacterial genes that are induced or up-regulated under continuous culture conditions defined by a dissolved oxygen tension of up to 10% air saturation measured at 37&#xb0; C. when compared with a dissolved oxygen tension of at least 40% air saturation measured at 37&#xb0; C. Said induced or up-regulated genes form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said induced or up-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Mycobacterial antigens expressed under low oxygen tension

A method is provided for identifying mycobacterial genes that are induced or up-regulated under culture conditions that are nutrient-starving and which maintain mycobacterial latency, said conditions being obtainable by batch fermentation of a mycobacterium for at least 20 days post-inoculation, when compared with culture conditions that are not nutrient-starving and which support exponential growth of said mycobacterium. Said induced or up-regulated genes form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said induced or up-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Mycobacterial antigens expressed during latency

A method is provided for identifying mycobacterial genes the expression of which is down-regulated during a stationary phase culture of mycobacteria under nutrient-starving conditions when compared with an exponential phase culture of mycobacteria under culture conditions that are not nutrient-starving and that support exponential growth of said mycobacteria. The described method optionally provides for identifying mycobacterial genes that are simultaneously down-regulated under low dissolved oxygen tension conditions. The down-regulated genes of the present invention form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said down-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Mycobacterial genes down-regulated during latency

A method is provided for identifying mycobacterial genes that are induced or up-regulated under culture conditions that are nutrient-starving and which maintain mycobacterial latency, said conditions being obtainable by batch fermentation of afor at least 20 days post-inoculation, when compared with culture conditions that are not nutrient-starving and which support exponential growth of said. Said induced or up-regulated genes form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuatedfor vaccines against mycobacterial infections. Similarly, peptides encoded by said induced or up-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Growing community of inventors

Salisbury, United Kingdom

Philip Marsh