Use of secreted/cell-bound poxvirus proteins (SPVP) and use thereof as vaccines and antiviral agents - Dr. Luis Sigal, DVM, PhD

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Developed by:

  • Luis J Sigal, DVM, PhD

  • Introduction:

    smallpox

    Smallpox, an epidemic viral disease caused by the highly pathogenic Orthopoxvirus variola, claimed more than 300 million lives from 1900 to 1978, when it was eradicated as a natural disease. Following eradication, most stocks of variola were destroyed and vaccination was discontinued. 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 to 40% in young children, 20% in adults, and 30% or more in the elderly). There are no currently available anti-viral measures to treat smallpox, but vaccination protects against this disease. 


    Smallpox

    ECTV type I IFN bp binds to mouse IFN-α with high affinity, blocks its biological activity in tissue culture, and complements Δ166 in vivo
    Xu et al. Journal of Experimental Medicine 2008:205:981-992 
    enlargement

    The vaccine used by the World Health Organization to eradicate naturally occurring smallpox disease is live vaccinia virus (VACV), which is normally weakly or non-pathogenic to humans but induces cross-protective immunity against other orthopoxviruses (OPVs). However, immunization with VACV 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 VACV vaccine is considered not safe, and antibodies to killed VACV are not effective at preventing the disease. Therefore, there is a need to develop a safe and effective smallpox vaccine.

    Smallpox

    OVPs, such as the variola virus (VARV, 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. Luis Sigal and his researchers have shown that one of these IRMs, the type I interferon binding protein (IFN bp) of ECTV, not only is 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.

    Advantages:

    Safe smallpox vaccine that does not use live viruses and is effective in immunodeficient people

    Citations:

    Relevant Articles:

    • 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," Neutralizing and Protective Antibodies Directed against Vaccinia Virus Envelope Antigens," Virology, (1999); 254(1): 71-80

    Related Technologies:

    Notes:

    Animal data available (see first article below)
    U.S. Provisional Patent Application