A study published online in Immunity reveals that by stimulating specialized immune cells to identify foreign cell membrane proteins that are shared across bacterial species, scientists may be able to develop vaccines with a broader reach. The researchers of the study from the Children’s Hospital of Pittsburgh of UPMS and the University of Pittsburgh School of Medicine say that this strategy could prove especially beneficial in preventing infections caused by multi-drug resistant organisms.
Senior author Jay K. Kolls, M.D., professor of pediatrics and immunology at the Pitt School of Medicine, as well as vice chair for translational research at the Department of Pediatrics and director of the Richard King Mellon Foundation Institute for Pediatric Research at the Children’s Hospital of Pittsburgh of UPMC explains that the genetic heritage of organisms like frogs, oysters and fish suggest, that a family of cell-signaling molecules named interleukin-17 (IL-17) progressed in evolution prior to the arrival of T cells, one of the main arms of the immune system in humans. The human IL-17 gene is switched on in a specialized group of immune cells in the T helper-cell lineage, which are known as Th17 cells.
Kolls continues:
“That development led us to think that perhaps Th17 cells confer some immunological advantage for eliminating infectious organisms beyond the antibody strategy that we typically employ when we make vaccines. We wanted to better understand what role Th17 cells play.”
In their study the researchers exposed mice to Klebsiella pneumoniae bacteria, a common cause of lung infection. When the mice had recovered from their first pneumonia several weeks later, the researchers re-exposed them and discovered that in both instances the presence of the germ resulted in higher numbers of Th17 cells in the mice’s lungs and spleen. However, when the researchers blocked IL-17, they discovered that the mice still developed immunity to infection, which indicates that the antibody response that is controlled by B cells did not need IL-17 to be activated.
They then infected mice that were bred to lack B cells, which produce antibodies, with Klebsiella pneumonia, and discovered that the mice had the potential to become immunized against repeat infection providing IL-17 was unblocked, which enabled Th17 cells to develop an immunological memory of the Klebsiella bacteria.
They also established that Th17 cells respond to protein complexes in the cell membrane the same as antibodies react to sugar complexes (polysaccharides) in the bacterial coat or capsule. According to Dr. Kolls, those proteins, which are integral to the structure of the cell membrane, are generally similar amongst bacterial strains contrary to the capsular polysaccharides, which are variable.
He continued saying:
“Some current vaccines require generating a response to a number of these capsular sugars for effective immunization. An approach that harnesses the stability of the Th17 cell response to common proteins has the potential to simplify vaccination and provide a broader spectrum of coverage. This strategy may be particularly useful against bacteria that have diverse capsular sugars or multi-drug resistant organisms.”
The U.S. Department of Health and Human Services Public Health Service funded the project with grants, which was also led by Kong Chen, Ph.D., and others from LSU Health Sciences Center and Children’s Hospital of Pittsburgh of UPMC, as well as researchers from the University of Queensland in Brisbane, Australia, and the University of Alabama in Birmingham.
Written by Petra Rattue