According to co-investigator Richard L. Gallo, MD, PhD, a dermatologist at the Veterans Affairs (VA) San Diego Health Care System and the University of California, San Diego, the finding may also lead to safer testing to identify those who should not receive the vaccine.
"Understanding the role of natural human antibiotics in diseases such as atopic dermatitis gives us a window into the possible reasons behind susceptibility to infections, and may help us better predict and control reactions to the smallpox vaccine or similar agents," said Gallo.
Gallo collaborated with a team at the National Jewish Medical and Research Center and Colorado Health Sciences Center that included lead investigator Michael D. Howell, PhD, and senior author Donald Y. M. Leung, MD, PhD.
In experiments in test tubes and mice, the researchers found that a germ-killing peptide called LL-37--largely absent from the skin of those with atopic dermatitis--selectively kills vaccinia, the living virus in the smallpox vaccine. The virus is a relatively benign cousin of variola, the virus in smallpox. The researchers believe LL-37 may be a key part of the normal immune response that allows vaccinia to confer immunity for smallpox but stops it before it can replicate and cause harm.
In 2002, a team including Gallo and Leung reported that people with atopic dermatitis (AD) are prone to recurring skin infections because they fail to produce germ-killing peptides known as beta-defensins and cathelicidins. These include "antimicrobial cathelicidin peptide," or LL-37. Peptides are groups of amino acids that link together to form proteins.
People with a history of even mild AD who receive the smallpox vaccine are at high risk for eczema vaccinatum, a condition in which the live virus in the vaccine spreads through the body and causes severe rashes over the area once affected by the eczema. This side effect is usually mild, but can be severe, and in rare cases, fatal. As a precaution, those with AD are advised to receive the vaccine only if they have already been exposed to the smallpox virus, since the disease itself is more dangerous.
Current U.S. policy calls only for lab or emergency workers who are more likely to be exposed to smallpox during a bioterrorist attack or other outbreak to receive the vaccine preventively. Others should receive it only after being exposed. The vaccine is effective both preventively and within a few days after exposure to the smallpox virus.
Initial plans last year called for up to 500,000 civilian health and emergency workers to receive the vaccine. But the initiative fizzled after a number of adverse reactions were reported, including at least three deaths. To date, fewer than 40,000 civilians have received the vaccine, and many hospitals have opted out of the program.
Of all Americans, about 25 percent, or 70 million people, are ineligible for the vaccine because of weakened immune systems, heart disease or other health issues. Even with these precautions, the Centers for Disease Control and Prevention estimate that for every million people who get the vaccine the first time, there could be 1,000 severe reactions and one or two deaths.
Up to 3 percent of American adults, and 17 percent of children, have AD. The chronic, hereditary disease is marked by red, itchy, swollen skin, and often accompanied by asthma and allergies. It accounts for about 1 in 6 dermatologist visits in the United States.
According to Gallo, who first discovered antimicrobial peptides in mammalian skin, a skin cream with LL-37 or similar peptides might be a potent remedy for eczema sufferers. His previous work with Leung and others has shown that the natural antimicrobial peptides in the skin work together to kill many common viruses, funguses and bacteria. Based on the latest study, the researchers believe a product with LL-37 might enable thousands of civilians or military personnel with atopic dermatitis to be vaccinated in the event of a bioterrorist attack with smallpox.
Gallo, Leung and Howell collaborated with James F. Jones, MD, Kevin O. Kisich, PhD, and Joanne E. Streib of the National Jewish Medical and Research Center and Colorado Health Sciences Center. Support for the study came from these institutions along with VA, the National Institutes of Health, Centers for Disease Control and Prevention, and American Academy of Allergy, Asthma and Immunology.
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