Nav: Home

Can we hypercharge vaccines?

April 21, 2016

BOSTON (April 21, 2016) - 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. (For inquiries, contact Abbie.Meyers@childrens.harvard.edu.) 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.
-end-
Kagan and first author Ivan Zanoni, PhD, are part of the Department of Gastroenterology at Boston Children's Hospital. Supporters of the study include the National Institutes of Health (grants AI093589, AI072955, P30 DK34854, 1R01AI121066-01A1 and HDDC P30 DK034854), Mead Johnson & Company, the Burroughs Wellcome Fund and the Cariplo Foundation.

About Boston Children's Hospital

Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 404-bed comprehensive center for pediatric and adolescent health care. Boston Children's is also the primary pediatric teaching affiliate of Harvard Medical School. For more, visit our Vector and Thriving blogs and follow us on our social media channels: @BostonChildrens, @BCH_Innovation, Facebook and YouTube.

Boston Children's Hospital

Related Immune Response Articles:

Discovering the early age immune response in foals
Researchers at the Cornell University College of Veterinary Medicine have discovered a new method to measure tiny amounts of antibodies in foals, a finding described in the May 16 issue of PLOS ONE.
Nixing the cells that nix immune response against cancer
For first time, study characterizes uptick of myeloid-derived suppressor cells in the spleens of human cancer patients, paving the way for therapies directed against these cells that collude with cancer.
Jumbled chromosomes may dampen the immune response to tumors
How well a tumor responds to immunotherapy may depend in part on whether its chromosomes are intact or in a state of disarray, a new study reports.
Tailored organoid may help unravel immune response mystery
Cornell and Weill Cornell Medicine researchers report on the use of biomaterials-based organoids in an attempt to reproduce immune-system events and gain a better understanding of B cells.
Tweaking the immune response might be a key to combat neurodegeneration
Patients with Alzheimer's or other neurodegenerative diseases progressively loose neurons yet cannot build new ones.
Estrogen signaling impacted immune response in cancer
New research from The Wistar Institute showed that estrogen signaling was responsible for immunosuppressive effects in the tumor microenvironment across cancer types.
No platelets, no immune response
When a virus attacks our organism, an inflammation appears on the affected area.
Malaria: A genetically attenuated parasite induces an immune response
With nearly 3.2 billion people currently at risk of contracting malaria, scientists from the Institut Pasteur, the CNRS and Inserm have experimentally developed a live, genetically attenuated vaccine for Plasmodium, the parasite responsible for the disease.
New finding will help target MS immune response
Researchers have made another important step in the progress towards being able to block the development of multiple sclerosis and other autoimmune diseases.
Flu infection reveals many paths to immune response
A new study of influenza infection in an animal model broadens understanding of how the immune system responds to flu virus, showing that the process is more dynamic than usually described, engaging a broader array of biological pathways.

Related Immune Response Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#520 A Closer Look at Objectivism
This week we broach the topic of Objectivism. We'll be speaking with Keith Lockitch, senior fellow at the Ayn Rand Institute, about the philosophy of Objectivism as it's taught through Ayn Rand's writings. Then we'll speak with Denise Cummins, cognitive scientist, author and fellow at the Association for Psychological Science, about the impact of Objectivist ideology on society. Related links: This is what happens when you take Ayn Rand seriously Another Critic Who Doesn’t Care What Rand Thought or Why She Thought It, Only That She’s Wrong Quote is from "A Companion to Ayn Rand"