Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Defective immune system response to smallpox vaccine detailed in new study

22.03.2006


People with Eczema may benefit from finding



Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have identified a defect in the immune response of people with the skin condition atopic dermatitis that puts them at risk of developing serious complications following smallpox vaccination. Led by Donald Y.M. Leung, M.D., Ph.D., of the National Jewish Medical and Research Center in Denver, the researchers used laboratory-grown human skin cells to show that an immune system protein called LL-37 is critical in controlling replication of vaccinia virus, the live virus that is the key component in standard smallpox vaccine.

The investigators are part of NIAID’s Atopic Dermatitis and Vaccinia Network, which was created in 2004 to integrate clinical and animal research aimed at reducing the risk of eczema vaccinatum, a potentially deadly complication of smallpox vaccination. Eczema vaccinatum occurs almost exclusively in people who have a history of atopic dermatitis, a common, non-contagious skin disorder also known as eczema.


"This new research, the first to be published by Atopic Dermatitis and Vaccinia Network scientists, illuminates one potential mechanism leading to eczema vaccinatum and improves our understanding of the immune responses to smallpox vaccine of people with atopic dermatitis," says NIAID Director Anthony S. Fauci, M.D.

Published in this month’s issue of Immunity, the study details how the overproduction in skin cells of inflammation-promoting molecules called interleukin-4 and interleukin-13 (IL-4 and IL-13) hampers LL-37 activity in people with atopic dermatitis. LL-37, a small protein produced in skin cells, is part of the body’s first line of defense against invaders. Earlier research by Dr. Leung and his colleagues suggested that LL-37 is critical in controlling the spread of vaccinia virus.

In the current study, the investigators used skin samples taken from people with atopic dermatitis (as well as samples taken from healthy volunteers without skin disease and from people with another skin condition called psoriasis) to further investigate how dysfunctions in the immune response of people with eczema set the stage for eczema vaccinatum. When exposed to vaccinia virus, the skin samples from healthy volunteers and from those with psoriasis reacted by producing more LL-37. As a result, the replication of the virus was controlled and eventually halted. In contrast, LL-37 production was minimal in skin samples from people with atopic dermatitis and vaccinia replication was poorly controlled. Next, the scientists exposed skin samples from people with atopic dermatitis to vaccinia, and then added LL-37. With the LL-37 supplement, the skin cells successfully controlled the viral replication.

Dr. Leung and his group then looked more closely at why vaccinia infection fails to induce LL-37 production in atopic dermatitis skin. Comparing immune responses of skin cells grown in the lab from healthy volunteers and from people with atopic dermatitis, the researchers found that the latter skin samples produced excessive amounts of IL-4 and IL-13. Adding IL-4 and IL-13 to skin cells from healthy volunteers prior to vaccinia exposure reduced levels of LL-37 production. Conversely, when the scientists applied IL-4- and IL-13-neutralizing antibodies to skin samples from people with atopic dermatitis, LL-37 production increased significantly.

Together, these findings suggest a rationale for new treatment approaches to eczema vaccinatum, notes Dr. Leung. One approach involves developing drugs to mimic the action of LL-37 or developing LL-37-containing creams that could be applied to the skin in order to boost its ability to contain vaccinia virus infection. Another approach could be to develop agents to neutralize IL-4 and IL-13. Although no such drugs are currently marketed, compounds that can neutralize IL-4 and IL-13 are under study as possible asthma and allergy treatments, Dr. Leung says, and might also be applied to eczema vaccinatum treatment.

Smallpox vaccine, which is made with live vaccinia virus (a close relative of the virus that causes smallpox), has not been routinely given in the United States since the early 1970s. But recent concerns about the possibility of a bioterrorist attack using smallpox virus prompted authorities to reinstate voluntary smallpox vaccination for specific groups, such as military personnel. In the first five months of 2003, the U.S. Department of Defense vaccinated more than 450,000 personnel against smallpox. During this period, the majority of those who deferred vaccination cited atopic dermatitis or other skin conditions as the main reason.

Anne A. Oplinger | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Studies and Analyses:

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>