Research Could Lead To Treatment That Would Help Stop A Smallpox Outbreak

"This is a very important finding because it has the potential to bean effective treatment for smallpox in humans and therefore could helpquickly stop a smallpox outbreak," said Mitchell Kronenberg, Ph.D, LIAIPresident. The finding is contained in a paper entitled "Vaccinia H3Lenvelope protein is a major target of neutralizing antibodies in humansand elicits protection against lethal challenge in mice" that waspublished in the September issue of the Journal of Virology. LIAIscientist Shane Crotty, Ph.D., a viral disease expert, led the team ofLIAI scientists which made the finding. Dr. D. Huw Davies and Dr. PhilFelgner of the University of California, Irvine Center for VaccineResearch were also major contributors.

Dr. Crotty and his team have discovered a protein in thesmallpox virus -- the H3 protein -- that elicits a particularly stronghuman antibody response. "Out of the 200 or so proteins contained inthe smallpox virus, we found that the H3 protein is a major target forantibodies that kill the virus," he said. No actual smallpox virus wasused in the studies in order to avoid any potential danger oftransmission.

Dr. Crotty made the findings by studying blood samples frompeople who had received the smallpox vaccine. "We used new techniquesthat we developed that made it easier to identify and isolateantibodies from the blood of immunized humans. Then we carefullyscreened for the antibodies that fight the smallpox virus," he said.The researchers then tested their findings by creating a batch of theanti-H3 protein antibodies, which they injected into mice. "We wereable to protect them from a strain of vaccinia pox virus that is verysimilar to smallpox and which is lethal to mice."

The National Institutes of Health is now funding furtherresearch by Dr. Crotty to better understand the molecular processessurrounding the finding. He said one focus of the research will be tofully develop anti-H3 antibodies in the lab that can be given tohumans. "We'll be working to further characterize and develop the useof this antibody as a treatment for smallpox," Dr. Crotty said.

The smallpox virus has been the subject of intense researchinterest worldwide in the last several years, prompted by bioterrorismconcerns. The virus was eradicated in the U.S. by 1950 and vaccinationsfor the general public were ended in 1972. But in the aftermath of9-11, new concerns have arisen that the smallpox virus could be used asa bioterrorist agent. Disease experts fear that samples of the smallpoxvirus may have fallen into the hands of terrorists at some point. Thisconcern has led to the creation of worldwide stockpiles of the smallpoxvaccine over the last several years.

Kronenberg said that if further study continues to validatethe safety and effectiveness of Dr. Crotty's finding, "we may one daysee high-quality batches of anti-H3 antibody stockpiled around theworld right along side the supplies of smallpox vaccine.

"While we do have a smallpox vaccine, there are concernsbecause people who are immuno-compromised cannot use the currentvaccine," he added, "including infants and the aged." Additionally, ifthere were a smallpox outbreak, there would be a certain time lapsebefore all people who have not been inoculated could receive thevaccine. Unlike the vaccine, the antibody would work to provideimmediate, although short-term protection, similar to how an antibiotictreats and for a short time protects against a bacterial infection.

"This makes Dr. Crotty's research even more interesting becausehis findings appear to offer a way to successfully treat the virus,"Kronenberg said. "This could be very important should people becomeinfected before they have a chance to be vaccinated."

About LIAI
Founded in 1988, the La Jolla Institute forAllergy and Immunology is a nonprofit medical research center dedicatedto increasing knowledge and improving human health through studies ofthe immune system. Scientists at the institute carry out researchsearching for cures for cancer, allergy and asthma, infectiousdiseases, and autoimmune diseases such as diabetes, inflammatory boweldisease and arthritis. LIAI's research staff includes more than 100Ph.Ds.