New York University

Other

Colorado State University Research Foundation

Suman Laal

Susan Zolla-Pazner

John T Belisle

Mark J Sartain

Provided are peptides suitable for early detection of active(Mtb) infection in immunocompromised individuals. The peptides can form complexes with antibodies directed to Mtb antigens MS, MPT51, ESAT6 or CFPIO. Also provided are methods for detected of complexes of the peptides and the antibodies. The presence of complexes aids in predicting risk in immunocompromised individuals of developing active tuberculosis.

Peptides offor a screening test for HIV positive patients at high-risk for tuberculosis

A number of peptide epitopes and fragments from three(Mtb) cell wall proteins have been identified as early antigens that induce antibodies early during Mtb infection in humans. The proteins are Proline-Threonine Repetitive Protein (PTRP), PE-PGRS51, and LipC. These peptides, alone or in mixtures, or as parts of fusion polypeptides or peptide multimers, are useful as antigens for serological detection of early in infection by detecting the presence of early antibodies against these proteins, thereby permitting earlier diagnosis of Mtb infection than was heretofore possible by conventional means. The above peptides and other peptide-based compositions are also used as immunogens for inclusion in TB vaccines. Also provided are methods for early diagnosis of Mtb infection and for immunizing a subject to prevent or treat Mtb infections and tuberculosis.

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A number of protein and glycoprotein antigens secreted by(Mtb) have been identified as 'early' Mtb antigens on the basis early antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. Epitope-bearing peptide fragments of these early Mtb antigens, in particular of an 88 kDa secreted protein, GlcB (SEQ ID NO:106) and of Mtb antigen MPT51 (SEQ ID NO:107) have been identified. These peptides, variants thereof, peptide multimers thereof that include two or more repeats of one or more of the peptides, and fusion polypeptides that include early Mtb antigenic proteins, peptides or both, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mtb antibodies. The antigenic proteins and peptides are also used in vaccine compositions.

Early detection of mycobacterial disease using peptides

Mycobacterial proteins from culture filtrate or cytosol are disclosed as being useful B cell antigens for early diagnosis of mycobacterial disease, particularly in humans. These proteins include four that had not previously been recognized as B cell antigens (LppZ protein encoded by Mtb gene Rv3006; SodC protein encoded by Mtb gene Rv0432; BfrB protein encoded by Mtb gene Rv3841 and TrxC protein encoded by Mtb gene Rv3914). Antigenic compositions include these proteins and/or peptide fragments thereof, in various combinations with each other or with one or more of a set of 10 additional Mtb proteins known to be antigens (in particular early antigens. Methods and kits for using these antigenic composition for early diagnosis of mycobacterial infection and disease are also disclosed.

Biomarkers of tuberculosis that distinguish disease categories: use as serodiagnostic antigens

A number of protein and glycoprotein antigens secreted by, or expressed on the surface of,(Mtb) have been identified as 'early' Mtb antigens on the basis of antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. PirG protein encoded by the Mtb gene Rv3810, PE-PGRS protein encoded by the Mtb gene Rv3367, PTRP protein encoded by the Mtb gene Rv0538) and MtrA protein encoded by the Mtb gene Rv3246c, or epitopes of these proteins, are useful in immunoassay methods or T cell assays for early, rapid detection of TB in a subject. Preferred immunoassays detect antibodies in the urine. Also provided are antigenic compositions, kits and methods useful for detecting these early Mtb antigens and early Mtb antibodies specific for them. Vaccine compositions comprising the foregoing antigens or epitopes are also disclosed.

Mycobacterial proteins as early antigens for serodiagnosis and vaccines

A number of protein and glycoprotein antigens secreted by (Mt) have been identified as &ldquo;early&rdquo; Mt antigens on the basis early antibodies present in subjects infected with Mt prior to the development of detectable clinical disease. These early Mt antigens, in particular an 88 kDa secreted protein having a pI of about 5.2 and the sequence of SEQ ID NO:106, which is present in Mt lipoarabinomannan-free culture filtrate, a protein characterized as Mt antigen 85C; a protein characterized as Mt antigen MPT51, a glycoprotein characterized as Mt antigen MPT32; and a 49 kDa protein having a pI of about 5.1, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mt antigen, an early Mt antibody, and immune complexes thereof. For the first time, a surrogate marker is available for inexpensive screening of individuals at heightened risk for developing advanced TB, in particular HIV-1 infected subjects and other immunocompromised individuals.

Early detection of mycobacterial disease

A number of protein and glycoprotein antigens secreted by,(Mt) have been identified as &ldquo;early&rdquo; Mt antigens on the basis early antibodies present in subjects infected with Mt prior to the development of detectable clinical disease. These early Mt antigens, in particular an 88 kDa secreted protein having a pI of about 5.2 present in Mt lipoarabinomannan-free culture filtrate, a protein characterized as Mt antigen 85C; a protein characterized as Mt antigen MPT51, a glycoprotein characterized as Mt antigen MPT32; and a 49 kDa protein having a pI of about 5.1, are useful in immunoassay methods for early, rapid detection of TB in a subject. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mt antigen, an early Mt antibody, and immune complexes thereof. For the first time, a surrogate marker is available for inexpensive screening of individuals at heightened risk for developing TB, in particular HIV-1 infected subjects and other immunocompromised individuals.

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Cortlandt Manor, NY, United States of America

Suman Laal