Researchers from the La Jolla Institute for Allergy & Immunology have pinpointed the cellular defect that increases the likelihood, among eczema sufferers, of developing eczema vaccinatum, a severe and potentially fatal reaction to the smallpox vaccine.
The research, conducted in mouse models, was funded under a special research network created by the National Institutes of Health in 2004. The network is working toward the development of a new smallpox vaccine that could be administered to the millions of Americans who suffer from atopic dermatitis, a chronic, itchy skin condition commonly referred to as eczema.
The La Jolla Institute's Toshiaki and Yuko Kawakami, M.D.s, Ph.D.s., a husband and wife scientific team, led the research group which found that activity levels of Natural Killer (NK) cells played a pivotal role in the development of eczema vaccinatum in the mice. The activity of the NK cells, which are disease fighting cells of the immune system, was significantly lower in the mice that developed eczema vaccinatum than in normal mice that also received the smallpox vaccine. This knowledge opens the door to one day developing therapies that could potentially boost NK cell activity in eczema sufferers.
"Since atopic dermatitis affects as many as 17 percent of children in the U. S. and since eczema vaccinatum carries a fatality rate of 5-10 percent, therapies that prevent or treat eczema vaccinatum successfully are crucial should the need for mass vaccination against smallpox arise in response to bioterrorism," said Harvard pediatrics professor Raif S. Geha, M.D., chief of immunology at Boston Children's Hospital and a principal investigator in the NIH funded network investigating eczema vaccinatum. "The discovery of the Kawakami team, who are participants in the NIH network, is an important step towards this goal."
People with active atopic dermatitis (eczema), or who have outgrown atopic dermatitis, and the people they live with currently cannot receive smallpox vaccinations because of the risk of eczema vaccinatum. While uncommon, eczema vaccinatum can develop when atopic dermatitis patients are given the smallpox vaccine or come into close personal contact with people who recently received the vaccine. It is estimated that a significant portion of the U.S. population is currently not eligible for smallpox vaccination.
"This discovery answers an important question that has long eluded the scientific community, "why people with atopic dermatitis were susceptible to developing eczema vaccinatum upon receiving the smallpox vaccine, while the general population was not," said Mitchell Kronenberg, the La Jolla Institute's president & scientific director. "It marks a significant advance toward the goal of ensuring that everyone can one day be protected against the smallpox virus."
The finding was published today in the online version of the Journal of Experimental Medicine in a paper entitled, "Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum." La Jolla Institute scientist Shane Crotty, Ph.D., also contributed to the study.