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Mycobacterium tuberculosis antigens Ag85A, Ag85B, and Rv3407 (Ag85A/B/Rv3407)

Target
Ag85A/B/Rv3407
Molecular classification
Enzyme (UniProt: P9WQP3), Antigen (PubMed: 21148483), Microbial protein (UniProt: P9WNK5)
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Overview

The Mycobacterium tuberculosis antigens Ag85A, Ag85B, and Rv3407 represent a specific combination of immunogenic proteins utilized in the development of recombinant tuberculosis vaccines, most notably the AERAS-402 (Ad35.TBS) candidate (PubMed: 21148483). Ag85A and Ag85B are members of the Antigen 85 complex, which are secreted mycolyltransferases essential for the synthesis of the mycobacterial cell wall by catalyzing the transfer of mycolic acids to arabinogalactan and the formation of trehalose dimycolate (UniProt: P9WQP3, P9WQP1). Rv3407 is a highly immunogenic protein identified as a potent T-cell antigen that is expressed during various stages of the M. tuberculosis life cycle, including latency (UniProt: P9WNK5). Together, these antigens are designed to elicit a robust Th1-mediated immune response, characterized by the activation of polyfunctional CD4+ and CD8+ T cells that produce protective cytokines (PubMed: 23935144). In clinical applications, they are typically delivered via viral vectors to boost the immunity provided by the traditional Bacille Calmette-Guérin (BCG) vaccine. The primary therapeutic goal is to enhance the host's ability to recognize and eliminate the pathogen, thereby preventing the progression from latent infection to active pulmonary tuberculosis (PubMed: 10888918).

Other names
Antigen 85AAntigen 85BRv3407FbpAFbpBFibronectin-binding protein AFibronectin-binding protein B85A85B
02

Mechanism of action

The mechanism involves the delivery of these antigens via a viral vector (such as Adenovirus 35) to host cells, which then express and present the Ag85A, Ag85B, and Rv3407 epitopes to the immune system. This process stimulates the expansion of antigen-specific CD4+ and CD8+ T lymphocytes that produce pro-inflammatory cytokines like IFN-gamma and TNF-alpha, which are critical for controlling Mycobacterium tuberculosis infection (PubMed: 21148483, 23935144).

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Biological functions

Cell wall biosynthesis (UniProt: P9WQP3)Mycolyltransferase activity (UniProt: P9WQP1)Immune response induction (PubMed: 21148483)T-cell activation (PubMed: 23935144)
04

Disease associations

Infection (PubMed: 21148483)Tuberculosis (PubMed: 21148483)
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Safety considerations

Injection site reactions (pain, swelling) (PubMed: 21148483)Systemic flu-like symptoms (fever, fatigue) (PubMed: 21148483)Pre-existing or induced anti-vector immunity (Ad35) (PubMed: 21148483)
06

Interacting drugs

AERAS-402 (Ad35.TBS) (PubMed: 21148483)
07

Biomarkers

Interferon-gamma (IFN-g) (PubMed: 21148483)Tumor Necrosis Factor-alpha (TNF-a) (PubMed: 23935144)Interleukin-2 (IL-2) (PubMed: 23935144)Polyfunctional CD4+ and CD8+ T-cell frequency (PubMed: 23935144)

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