Researchers at Oregon Health & Science University have been awarded a $3 million grant from the Bill & Melinda Gates Foundation to study whether a particular group of infection-fighting cells, known as T cells, may be viable for the development of a vaccine aimed at combatting the global tuberculosis epidemic.
The funding was awarded to David Lewinsohn, M.D., Ph.D., in the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital. Lewinsohn will expand on previous findings that revealed a population of TB-recognizing T cells known as mucosa associated invariant T (MAIT). Due to their reliance on a common antigen recognition system, and their abundance in the human lung, researchers believe that MAIT cells may be harnessed as unconventional TB vaccine targets.
According to the World Health Organization’s 2015 global report, TB claimed 1.5 million lives in 2014 — 140,000 of which were children — making it the leading cause of death worldwide. TB is a contagious airborne disease caused by the bacteria Mycobacterium tuberculosis. It generally attacks the lungs, though may spread to various parts of the body such as the kidney, spine and brain.
“Improved TB vaccines will require an understanding of the mechanisms by which T cells recognize other cells infected with Mtb, particularly in the lung,” said Lewinsohn, a professor of pulmonary and critical care medicine, and pediatrics in the OHSU School of Medicine, and staff physician at the VA Portland Health Care System. “This grant from the Gates Foundation represents a continued commitment toward the eradication of TB. We are excited to be a part of it.”
The research approach focuses on a combination of T cell biology, mass spectrometry and protein chemistry to precisely define the molecular structure of MAIT cell antigens, a substance that causes your immune system to respond. The objective is to create stable immunogens, or antigens capable of creating an immune response, which will be suitable for vaccination in nonhuman primates and, eventually, humans. Lewinsohn’s team will use flow cytometry as well as mass spectrometric cytometry, or CyTOF, to define the full spectrum of MAIT cell characteristics in both nonhuman primates and humans that, in turn, will enable future vaccine studies. Further, this grant will allow the development of high-quality mouse models for future testing of MAIT cell vaccines.
This three-year research project brings together collaborators from OHSU, the University of Chicago, the University of Oklahoma Health Sciences University, Colorado State University, La Jolla Institute of Allergy and Immunology, and Stanford University.