As thin as it is, your skin could provide powerful protection against disease thanks to a new vaccine technique, dermatology researchers report. The finding from a mouse study may lead to more effective vaccines against a variety of diseases including melanoma, HIV, malaria, and tuberculosis, the researchers say.
The skin is the body's first line of defense against disease, but researchers have debated just how the skin responds to invasion by aggressive germs. When foreign organisms enter the skin, dendritic cells capture them and alert the body's watchdog T cells. The idea is that dendritic cells present T cells with an antigen, a molecular wanted poster with which to identify and kill infected cells. But current vaccine techniques have failed to incite skin dendritic cells to ward off disease, leading some immunologists to question their importance. Some have suggested that skin dendritic cells don't actually prime the immune system but instead pass that work off to related cells in the lymph node. The new study shows, finally, how to get a rise out of dendritic cells to produce a potent immune response.
Dermatology researchers Louis Falo Jr. and Yukai He of the University of Pittsburgh in Pennsylvania packed RNA that encodes for a melanoma tumor antigen into a virus known as a lentivirus. They injected the lentivirus vaccine into the foot pads of the mice and observed that skin dendritic cells captured the foreign vaccine organism and migrated to the lymph nodes, where they primed T cells for attack against melanoma tumors. Cultured samples from the lymph nodes revealed that although dendritic cells from both the skin and the lymph node were present, the skin dendritic cells had presented the antigen to the T cells. The mice responded by fighting and killing melanoma cells for as long as 4 months after a single vaccination, whereas mice injected with a control lost their ability to fight melanoma cells after 1 month, the researchers report in the May issue of the journal Immunity. "It was surprising to see the duration of the immune response after just one immunization," Falo says.
The key to this strong response was the packaging. The lentivirus "vector" delivered instructions for making the tumor antigen to the skin dendritic cells but did not kill them or change their function, as had other vectors. He says the researchers hope to win approval to use the vector in clinical trials, thereby harnessing the natural protective power of the skin to fight HIV and other diseases.
"The end result of the study is, 'hey it's the vector stupid,' " says Chris Norbury, an immunologist at Pennsylvania State University in State College. The evidence that skin dendritic cells are responsible for priming the T cells was convincing, Norbury said, but the researchers stopped short of tracking individual cells from the skin to the T-cell priming stage.
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