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Can we hypercharge vaccines?

Tapping a chemical we already make could enhance T-cell production

Date:
April 21, 2016
Source:
Boston Children's Hospital
Summary:
Researchers report that a fatty chemical naturally found in damaged tissues can induce an unexpected kind of immune response, causing immune cells to go into a 'hyperactive' state that is highly effective at rallying infection-fighting T-cells. The findings could enhance vaccines and make them much more effective.
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Researchers at Boston Children's Hospital report that a fatty chemical naturally found in damaged tissues can induce an unexpected kind of immune response, causing immune cells to go into a "hyperactive" state that is highly effective at rallying infection-fighting T-cells. The findings, published online by Science on April 21, could enhance vaccines and make them much more effective.

The researchers, led by Jonathan Kagan, PhD, got a five times greater adaptive immune response in mice when using the chemical, called oxPAPC. They believe that oxPAPC or a related synthetic compound could be used to help immunize people against a wide range of infections. "We think this could be a general means to increase response to any type of vaccine," says Kagan, also an associate professor at Harvard Medical School.

oxPAPC targets only dendritic cells -- sentinels that circulate around the body searching for microbes and activating T-cells to destroy the invaders. Previously, it was thought that dendritic cells (also commonly known as antigen-presenting cells) have just two states: an inactive state, in which they can search for microbes, and an active state, in which they have encountered a microbe and gain the ability to activate T-cells.

"We identified a naturally-occurring molecule that creates a heightened, 'hyperactive' state of dendritic cell activation," says Kagan. "These hyperactive cells live for a long time and are the best activators of T-cells that we know of, so this could be a very useful tool in vaccine development."

In particular, when they gave oxPAPC to mice, they saw strong activation of memory T-cells. Memory T-cells respond more effectively to invaders than other kinds of T-cells, but are not efficiently elicited by ordinary activated dendritic cells.

Kagan's team further showed that hyperactivated dendritic cells make a critical protein, IL-1ß, that triggers memory T-cell production. Dead dendritic cells also release IL-1ß, but only for a short period of time. Hyperactivated dendritic cells produce IL-1ß for longer times, which likely explains why they are such effective stimulators of memory T-cells.

Finally, the researchers found that oxPAPC's key target is an enzyme called caspase-11. When activated by other molecules, caspase-11 triggers cell death and inflammation. But when activated by oxPAPC, the enzyme promotes hyperactivation of dendritic cells.

"These discoveries highlight that dendritic cells and caspase-11 can have more than one activation state, which was never before known," says Kagan.

Kagan and Boston Children's Hospital's Technology and Innovation Development Office (TIDO), have filed for a patent on this work and are seeking investor interest so they can move oxPAPC or a similar compound toward a clinical trial. While the work was in mice, Kagan notes that other studies have shown that the biology of dendritic cells is similar in mice and humans.


Story Source:

Materials provided by Boston Children's Hospital. Note: Content may be edited for style and length.


Journal Reference:

  1. I. Zanoni, Y. Tan, M. Di Gioia, A. Broggi, J. Ruan, J. Shi, C. A. Donado, F. Shao, H. Wu, J. R. Springstead, J. C. Kagan. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science, 2016; DOI: 10.1126/science.aaf3036

Cite This Page:

Boston Children's Hospital. "Can we hypercharge vaccines? Tapping a chemical we already make could enhance T-cell production." ScienceDaily. ScienceDaily, 21 April 2016. <www.sciencedaily.com/releases/2016/04/160421150052.htm>.
Boston Children's Hospital. (2016, April 21). Can we hypercharge vaccines? Tapping a chemical we already make could enhance T-cell production. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/04/160421150052.htm
Boston Children's Hospital. "Can we hypercharge vaccines? Tapping a chemical we already make could enhance T-cell production." ScienceDaily. www.sciencedaily.com/releases/2016/04/160421150052.htm (accessed May 23, 2017).

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