To be able to work properly, the immune system needs to be able to tell the difference between live and dead cells, and it does this by using a damaged cell-recognition molecule called Clec9A. Researchers are looking into harnessing this ability to "trick" the immune system and help make a safer and more effective vaccine.
Clec9A is on the surface of the subset of dendritic cells (a type of immune cell, also known as antigen presenting cells) that are responsible for the cleaning up and tidying away of the dead cells, and for presenting parts of these cells so that other immune cells can recognize the foreign invaders and respond. According to new research from the Walter and Eliza Hall Institute of Medical Research, the molecule recognizes molecules from inside the cells that are only exposed when the cell membranes are damaged through injury or infection.
"In this study we discovered that Clec9A recognizes and binds to fibers of actin, internal cell proteins that are found in all cells of the body. Actin is only exposed when the cell membrane is damaged or destroyed, so it is an excellent way of finding cells that could harbor potentially dangerous infections and exposing them to the immune system," said Dr. Mireille Lahoud, now at the Burnet Institute.
According to the researchers, creating vaccines that bind to Clec9A could trick dendritic cells into thinking they have encountered a damaged cell and help to launch an immune response to the vaccine, cutting the amount of vaccine needed a hundredfold to a thousandfold, explained professor Ken Shortman of the Immunology division. "Traditional vaccine technology for generating immunity, such as using inactivated whole viruses or parasites for immune recognition, requires large amounts of vaccine in the hopes it will encounter the correct immune cells, and incorporates other substances (adjuvants) that are needed to signal to the immune system that something foreign is happening. We are proposing a new type of vaccine that we know will head directly to the right cell to help stimulate an immune response, and doesn't cause the same side effects because it is more specific."
This approach could be used to create prophylactic vaccines against traditionally difficult targets, or to support the development of therapeutic vaccines.
- read the press release
- see the abstract