Methods for Dagnosing and Treating Mycobacterium tuberculosis (Mtb) Infection through Detection of CD153 Expression Level.


Mycobacterium tuberculosis (Mtb) infection continues to be the leading cause of death due to a single infectious agent and poses significant global health challenges. Past research has shown that CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFN(γ) production is the primary mechanism of CD4 T cell-mediated protection.

NIAID researchers have discovered that the expression of TNF superfamily molecule CD153 (TNSF8) is required for control of the pulmonary Mtb infection by CD4 T cells. The results have shown that, in Mtb infected mice, CD153 expression is highest on Ag-specific Th1 cells in the lung tissue parenchyma. On the contrary, CD153 deficient mice have developed high pulmonary bacterial loads and succumb early to Mtb infection. In Mtb infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to the blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. Further, in Mtb infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active TB. Since the expression of CD153 by CD4 T cells is a major immune mechanism of host protection against Mtb infection, the discovery can be used to effectively diagnose and treat Mtb infections in the future.

Potential Commercial Applications: Competitive Advantages:
  • Mycobacterium tuberculosis diagnostic that measures the production of CD153 as an indicator of the disease and its severity
  • A companion diagnostic can be used to determine the effectiveness of a vaccine against a Mycobacterium tuberculosis infection in a subject
  • Therapeutic use to treat Mycobacterium tuberculosis in a subject
 
  • Ability to be used as a target for Mtb diagnostics and therapeutics


Inventors:

Daniel Barber (NIAID)  ➽ more inventions...

Michelle Sallin (NIAID)  ➽ more inventions...

Keith Kauffman (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 62/633,816

Publications:
Sallin, Michelle A., et al. PMID: 30202016

Collaboration Opportunity:

The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the methods of treating human tuberculosis. For collaboration opportunities, please contact James M .Robinson at james.robinson4@nih.govor 1-301-761-7542.


Licensing Contact:
James Robinson,
Email: james.robinson4@nih.gov
Phone: 301-761-7542

OTT Reference No: E-085-2018-0
Updated: Nov 9, 2018