"This is a very important finding because it has the potential to be an effective treatment for smallpox in humans and therefore could help quickly stop a smallpox outbreak," said Mitchell Kronenberg, Ph.D, LIAI President. The finding is contained in a paper entitled "Vaccinia H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice" that was published in the September issue of the Journal of Virology. LIAI scientist Shane Crotty, Ph.D., a viral disease expert, led the team of LIAI scientists which made the finding. Dr. D. Huw Davies and Dr. Phil Felgner of the University of California, Irvine Center for Vaccine Research were also major contributors.
Dr. Crotty and his team have discovered a protein in the smallpox virus – the H3 protein -- that elicits a particularly strong human antibody response. "Out of the 200 or so proteins contained in the smallpox virus, we found that the H3 protein is a major target for antibodies that kill the virus," he said. No actual smallpox virus was used in the studies in order to avoid any potential danger of transmission.
Dr. Crotty made the findings by studying blood samples from people who had received the smallpox vaccine. "We used new techniques that we developed that made it easier to identify and isolate antibodies from the blood of immunized humans. Then we carefully screened for the antibodies that fight the smallpox virus," he said. The researchers then tested their findings by creating a batch of the anti-H3 protein antibodies, which they injected into mice. "We were able to protect them from a strain of vaccinia pox virus that is very similar to smallpox and which is lethal to mice."
The National Institutes of Health is now funding further research by Dr. Crotty to better understand the molecular processes surrounding the finding. He said one focus of the research will be to fully develop anti-H3 antibodies in the lab that can be given to humans. "We'll be working to further characterize and develop the use of this antibody as a treatment for smallpox," Dr. Crotty said.
The smallpox virus has been the subject of intense research interest worldwide in the last several years, prompted by bioterrorism concerns. The virus was eradicated in the U.S. by 1950 and vaccinations for the general public were ended in 1972. But in the aftermath of 9-11, new concerns have arisen that the smallpox virus could be used as a bioterrorist agent. Disease experts fear that samples of the smallpox virus may have fallen into the hands of terrorists at some point. This concern has led to the creation of worldwide stockpiles of the smallpox vaccine over the last several years.
Kronenberg said that if further study continues to validate the safety and effectiveness of Dr. Crotty's finding, "we may one day see high-quality batches of anti-H3 antibody stockpiled around the world right along side the supplies of smallpox vaccine.
"While we do have a smallpox vaccine, there are concerns because people who are immuno-compromised cannot use the current vaccine," he added, "including infants and the aged." Additionally, if there were a smallpox outbreak, there would be a certain time lapse before all people who have not been inoculated could receive the vaccine. Unlike the vaccine, the antibody would work to provide immediate, although short-term protection, similar to how an antibiotic treats and for a short time protects against a bacterial infection.
"This makes Dr. Crotty's research even more interesting because his findings appear to offer a way to successfully treat the virus," Kronenberg said. "This could be very important should people become infected before they have a chance to be vaccinated."
Founded in 1988, the La Jolla Institute for Allergy and Immunology is a nonprofit medical research center dedicated to increasing knowledge and improving human health through studies of the immune system. Scientists at the institute carry out research searching for cures for cancer, allergy and asthma, infectious diseases, and autoimmune diseases such as diabetes, inflammatory bowel disease and arthritis. LIAI's research staff includes more than 100 Ph.Ds.
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