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Secreted/Cell Bound Poxvirus Proteins and Methods of Use Thereof as Vaccines and Antiviral Agents
Poxviridae comprise a large family of complex DNA viruses that replicate in the cytoplasm of vertebrate and invertebrate cells. An epidemic poxvirus infection in humans was smallpox, caused by the highly pathogenic variola virus, a member of the genus Orthopoxvirus. The World Health Organization declared the global eradication of smallpox in 1980. Smallpox now exists mainly in laboratories. In the past few years, concerns have been raised that stocks of variola virus could be expanded and used as a bioweapon, a threat that would be devastating in an unvaccinated population. The overall mortality rate for smallpox in unvaccinated people is 30-40% in young children, 20% in adults, and 30% or more in the elderly. Additionally, certain poxvirus infections cause great damage to livestock and wild life populations and are often require costly eradication procedures.
The vaccine used by the World Health Organization to eradicate naturally occurring smallpox disease was live vaccinia virus another member of the genus Orthopoxvirus. Vaccinia virus is weakly pathogenic or non-pathogenic to humans but induces cross-protective immunity against other members of Orthopoxvirus. However, immunization with vaccinia virus is not recommended for the millions of people who are at increased risk and have immune deficiencies, eczema, atopic dermatitis and heart disease. As a result, the live vaccinia virus vaccine is not considered safe, and antibodies to killed vaccinia virus are not effective at preventing the disease. Therefore, there is a need to develop a safe and effective smallpox vaccine.
Summary of the Invention
Orthopoxviruses (OPVs), such as the variola virus (agent of smallpox) and the murine equivalent ectromelia virus (ECTV, agent of mousepox), encode immune response modifiers (IRMs) that can increase virulence by decreasing the host immune response. Dr. Sigal and his researchers have shown that one of these IRMs, the Type I Interferon Binding Protein (IFN bp) of ECTV, is not only essential for ECTV virulence but is a natural target of the antibody response, and that immunization with recombinant Type I IFN bp protects mice from lethal mousepox. Thus, this discovery provides the framework for a novel approach to anti-viral vaccination. Combining essential IRMs and structural proteins in new vaccine formulations may be the best approach for an effective and safer subunit vaccine to OPVs and possibly other viruses.
Safe smallpox vaccine that does not use live virus and is effective in immunodeficient people
Xu RH, Cohen M, et al., "The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination," J Exp Med, 2008 Apr 14; 205(4): 981-92
Fang M, Cheng H, et al., "Immunization with a single extracellular enveloped virus protein produced in bacteria provides partial protection from a lethal orthopoxvirus infection in a natural host," Virology, (1999); 254(1): 71-80
US Patent # US 8,557,241 B2 issued October 15, 2013