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Chimp, Human Antibody Hybrid Could Fight Smallpox By Chris Schneidmiller WASHINGTON — A treatment combining human and chimpanzee antibodies could be used to reduce the side effects of the smallpox vaccine, or to counter the disease itself, researchers said in an article published this week (see GSN, Dec. 7, 2005). The smallpox vaccine now stockpiled in the United States has been found to cause potentially fatal complications for people suffering from impaired immune systems or skin conditions such as eczema. Pregnant women and children less than 12 months in age also could be put at risk by receiving the vaccine. Vaccinia immune globulin (VIG) — antibodies collected from the blood of people who have received the smallpox vaccine — is now used to treat complications from inoculation. However, the eradication of naturally occurring smallpox has resulted in limited stocks of the globulin, which also in rare instances could carry other viral agents to recipients. A team of scientists led by the researchers from the National Institute of Allergy and Infectious Diseases reported a possible answer to the dilemma in the Proceedings of the National Academy of Sciences. Researchers found that the hybrid human-chimpanzee antibodies in test-tube experiments blocked the spread of the variola virus that causes smallpox and the vaccinia virus used in the vaccine, according to an NIAID release. While the smallpox vaccine might take a week or more to take effect, antibodies — proteins that neutralize viruses and bacteria — go to work immediately. That could be crucial for safeguarding the health of unvaccinated people exposed to the pathogen in a bioterror incident, researcher Robert Purcell, co-head of the NIAID Laboratory of Infectious Diseases, said in an interview. “This is an important finding in the race to develop effective measures against a potential bioterror attack involving the deadly smallpox virus,” Elias Zerhouni, director of the National Institutes of Health, said in the release. “This study shows that there are potential alternatives to existing treatments and perhaps to existing vaccines that we can use to enhance our arsenal of medical countermeasures.” Purcell said this project, like many others, began as fears of biological terrorism grew following the Sept. 11, 2001, attacks. Using chimpanzee antibodies offers the opportunity to develop a stronger countermeasure than simply using human samples. The two species’ antibodies are “virtually identical,” Purcell said. However, chimpanzees in experiments are given a stronger strain of vaccine than generally used in humans, which creates a “more robust” antibody, he said. Researchers collected antibodies taken from the bone marrow of two chimpanzees that had received the smallpox vaccine. They then combined those antibodies with a human antibody to create two hybrids. Both hybrid types blocked the spread of the vaccinia virus in test-tube work, while one eliminated a strain of the smallpox virus. The scientists then moved on to experiments with mice. The hybrids protected the animals from weight loss after they were exposed to the vaccinia virus, while a control group of mice that received no protection suffered weight loss corresponding to the reproduction of the virus in their lungs. Mice injected with vaccinia survived after receiving varying doses of one of the hybrid antibodies or a 5-microgram dose of vaccinia immune globulin. All five mice in the control group that received no treatment died or were euthanized after losing 70 percent of their weight, according to the press release. Mice injected with one 90-microgram dose of hybrid antibody 48 hours after exposure to smallpox lost a small amount of weight but quickly recovered. Mice that received the globulin after the same time delay lost significantly more weight. “Our antibodies were considerably better than the VIG,” Purcell said. The hybrid antibodies need to be tested in another animal model against monkeypox, which is similar to smallpox but less virulent in humans, Purcell said. The Food and Drug Administration generally requires testing of two different animals for drugs that cannot be tested in humans, Purcell said. He could not say when the hybrid antibody might be approved for public use. “It’ll be up to the government to decide what they want to do with it,” he said.
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