Vaccinia Antigens for Development of a Smallpox Vaccine
Introduction Smallpox is a disease of increasing biodefense importance. The current smallpox vaccine is too virulent, and therefore unsafe, for up to 5% to 10% of the American public. Vaccinia are viruses that are genetically related to smallpox and inoculation with live, replicationcompetent vaccinia leads to mild, transitory infection and the immune memory provoked then prevents smallpox. Infection with the current generation of live vaccinia vaccine has toxic side effects in some individuals, motivating a search for safer alternative vaccines. Monkeypox is a related virus that causes deadly disease in Africa and occasional outbreaks in the US. A number of specific antigenic fragments encoded by the vaccinia genome that elicit a cytotoxic CD8+ T-cell immune memory response have been identified. Along with neutralizing antibodies, it is likely that CD8 T-cell memory is functionally important in the prevention of smallpox. Technology description Researchers at the UW have documented more than a dozen vaccinia antigens, and epitopes within these antigens, that elicit CD8 T cell responses in humans. The epitopes identified could be used in the preparation of subunit vaccines for prevention of smallpox and monkeypox. In addition, these epitopes may provide test reagents for the immunogenicity testing of candidate vaccines. Business opportunity Although smallpox was eradicated from circulation in the community in 1980, the virus has reemerged as a healthcare concern because of its bioterrorism potential. Because little or no natural immunity exists today, the WHO suggests that, in most communities, 90% of the population is fully susceptible to smallpox. The fatality rate, which historically was around 30%, could well be higher if the disease were to reemerge. Though vaccination with the currently available smallpox vaccine provides high level immunity, some people are at greater risk for serious side effects. As such there is still a need for a novel smallpox vaccine. There is also a need to test other candidate smallpox vaccines under evaluation for clinical deployment. The antigens discovered by UW researchers are rational candidates for inclusion in a subunit vaccine or for use as test reagents in the evaluation of other candidate vaccines. Discovery of new antigens and further characterization of epitopes is ongoing. Intellectual property position The UW has applied for patent protection to secure the rights to this technology. Related Publication(s)Diversity in the acute CD8 T cell response to vaccinia virus in humans. J Immunol. 2005 Dec 1;175(11):7550-9.
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