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    Next-Generation Vaccines: Tricking The Immune System
    By News Staff | April 5th 2012 08:30 PM | 3 comments | Print | E-mail | Track Comments
    A protein found on the surface of immune cells called dendritic cells recognizes dangerous damage and trauma that could signify infection. Dendritic cells are critical for raising the alarm about the presence of foreign invaders in the body such as viruses, bacteria and parasites as well as tumor cells and other dead or damaged cells. Also known as antigen-presenting cells, they digest and present molecules from damaged cells to other immune cells that recognize foreign invaders and launch an immune response.

    This discovery of how a vital immune cell recognizes dead and damaged body cells could modernize vaccine technology by 'tricking' cells into launching an immune response, leading to next-generation vaccines that are more specific, more effective and have fewer side-effects because the immune system has evolved a very clever way of detecting damaged and dead cells to help promote an immune response.

    "Dr Irina Caminschi and I previously identified a protein called Clec9A (C-type lectin domain family 9A) that sits on the surface of specialised types of dendritic cells and responds to damaged and dying cells," said Dr Mireille Lahoud. "In this study we discovered that Clec9A recognises and binds to fibres 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 harbour potentially dangerous infections and exposing them to the immune system."

    Shortman said that exploiting Clec9A could be used to generate a new, more modern class of vaccines that are more effective and have fewer side-effects. "The Clec9A protein is one of the best targets currently known for improving immune responses," he said. "By creating vaccines that bind to Clec9A, we can trick dendritic cells to think they have encountered a damaged cell and help to launch an immune response to the infectious agent of our choice."

    Shortman said targeting Clec9A could decrease the amount of vaccine needed by 100 to 1000 times. "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," Professor Shortman said.

    Lahoud said that the finding could develop or increase the efficacy of vaccines for diseases that do not currently have good preventive options, such as malaria, or HIV. "There is also the possibility that the system could be used to develop therapeutic vaccines for treating diseases, such as some forms of cancer, as well as for preventing them," she said.


    Published in Immunity.

    Comments

    Gerhard Adam
    On the other hand, if we screw something up, then we could end up with a generalized immune response to healthy tissue and kill the patient.

    ... and for all those that think this "precautionary principle" is simply anti-science, consider that this is a technological implementation and not science.  As with all of our technological implementations problems have invariably occurred, which resulted in us learning more and getting better and better and such exploitation.

    So when the Tacoma Narrows bridge came down, it wasn't because we didn't know how to build bridges, nor that we didn't understand the physics of standing waves.  It just never occurred to us that this could happen as it did.  Similarly I'm only concerned that when we are operating in systems that are vastly more complex, that we don't create a new "Tacoma Narrows Bridge" incident that isn't nearly as easy to recover from.
    Mundus vult decipi
    I'm right there with you Gerhard!

    There was one thing left out of this discussion of what happens when a dendritic cell (DC) eats a dead cell. There are actually one of two fates. Either the DC process and present immunogenic antigens from the dead cell to responding T cells or it does not and possibly as a result to that begin to secrete something that is immunosuppressive called IDO. That decision has to do with how the dead cell died. I do agree that this is an important finding, but I really wished that the scientist who talked about would have put the whole thing into the context of what really happens when a DC decides to eat a dead cell.