Children's Hospital Boston receives more than $10 million to help make smallpox vaccine safer


Researchers to investigate severe skin reaction, a barrier to large-scale immunization

Children's Hospital Boston (CHB) has secured contracts totaling nearly $10.5 million through the National Institutes of Health to study a potentially life-threatening complication of smallpox immunization known as eczema vaccinatum (EV). The goal is to reduce the risk of EV and develop a safer smallpox vaccine.

EV is a severe skin infection caused by vaccinia, the live virus used in the smallpox vaccine. The risk of EV has been a major barrier to reintroducing widespread smallpox immunization. Routine vaccination ended in the U.S. in 1972, so many Americans lack immunity to smallpox, which is now seen as a potential weapon of bioterrorism.

Most susceptible to EV are the millions of Americans, including many young children, who have a history of atopic dermatitis, the allergy-related skin condition better known as eczema. People with weakened immune systems also are at risk. If not treated in time, EV has a mortality rate of up to 6 percent, and as high as 30 percent among children under age 2.

CHB's Division of Immunology will play a leading role in a nationwide research network, launched by the National Institute of Allergy and Infectious Diseases (NIAID), that will investigate why atopic dermatitis predisposes smallpox vaccine recipients to EV.

"Since 5 percent of kids and about 1 percent of adults have atopic dermatitis, the risk is great should a decision be made to mass vaccinate," says Dr. Raif Geha, chief of Immunology at CHB. "EV can develop even in people with mild atopic dermatitis, as well as healthy people who had atopic dermatitis in the past. Also, since the virus in the smallpox vaccine is live, it can spread from contact with people who have been vaccinated."

Geha will head up the Animal Studies Consortium under the contract, coordinating animal studies at CHB and five subcontracting institutions under a five-year, $10 million grant. Geha's own lab will establish a mouse model for atopic dermatitis, explore different components of the immune response to the vaccinia virus used in smallpox vaccine, seek biochemical factors that predispose mice to EV, and test possible preventive therapies. The researchers hypothesize that an abnormal immune response in the skin makes people with atopic dermatitis susceptible to EV after smallpox vaccination. Dr. Hans Oettgen, clinical director of Immunology at CHB, will use animal models to further examine the role of skin abnormalities. His team will compare immune responses to the vaccinia virus with responses to two other viruses: herpes simplex virus, which also causes severe skin infections, and yellow fever virus, which infects via the skin, but does not cause skin disease.

Dr. Lynda Schneider, director of the Allergy Program at CHB, will be one of six principal investigators in the Clinical Studies Consortium. Under a three-year grant of approximately $450,000, her team will investigate the immune response to vaccination with live varicella virus, a less harmful skin virus that causes chickenpox and shingles. Children with and without atopic dermatitis will receive live varicella vaccine and undergo a battery of lab tests three weeks later. Varicella will act as a surrogate for vaccinia, yielding clues about how atopic dermatitis may alter the immune response to live virus vaccines.

Understanding the relationship between atopic dermatitis and EV is important because atopic dermatitis is so common, with the highest prevalence in young children. During the 1960s, when smallpox vaccine was still being given, EV was estimated to cause 10 to 39 cases of EV per million people vaccinated. Today, the potential number of cases is believed to be much higher, since atopic dermatitis has become much more prevalent in the population.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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