Colorado State University Research Foundation

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

New York University

New York Medical College

John T Belisle

Suman Laal

Susan Zolla-Pazner

Gary P Wormser

Claudia R Molins

Ian M Orme

Sebabrata Mahapatra

Mark J Sartain

The present disclosure provides a biosignature that distinguishes Lyme disease, including early Lyme disease, from STARI. The present disclosure also provides methods for detecting Lyme disease and STARI, as well as methods for treating subjects diagnosed with Lyme disease or STARI.

Differentiation of lyme disease and southern tick-associated rash illness

The present disclosure provides methods for detecting early Lyme disease. The present disclosure provides a biosignature indicative of the presence or absence ofinfection.

High sensitivity method for early Lyme disease detection

A method for metabolomically evaluating a subject's response to an anti-mycobacterial agent. The method includes the steps of generating multiple small molecule profiles using samples collected from the subject at or immediately prior to the start of treatment and at a times subsequent to the start of treatment with the anti-mycobacterial agent, identifying predetermined biomarkers in the small molecule profiles of the subject and comparing to a known standard established for the agent as an indication of whether the human is benefiting from treatment with the agent. Also provided are methods of monitoring treatment compliance, methods for establishing biomarkers indicative of treatment efficacy and validated biomarkers shown to be effective in assessing efficacy of anti-tuberculosis drugs.

Markers for screening anti-mycobacterial treatment efficacy

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

Vaccine compositions for boosting immunity to mycobacteria when administered in mid-life in a subject who has been vaccinated neonatally or in early childhood with BCG and in whom protective immunity has waned comprise one or more purified immunogenic proteins fromfrom a group of 30 proteins that stimulate T cell immunity and interferon-&#x3b3; secretion. A preferred protein is Ag85A, the secreted product (SEQ ID NO:31) of the Rv3084c gene. Also disclosed are methods for boosting immunity in such BCG-vaccinated subjects comprising administering an effective amount of the above vaccine composition.

Mid-life vaccine and methods for boosting anti-mycobacterial immunity

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.

Growing community of inventors

Fort Collins, CO, United States of America

John T Belisle