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| Recombinant Vaccinia Viruses Expressing IL-15 and Methods of Using the Same
Vaccinia-based vaccines have a proven record of being effective vaccines in humans as well as in animals. However, accumulating evidence reveals the need for technology to improve the immune responses such vaccines generate.
The present invention discloses recombinant vaccinia viruses capable of expressing interleukin 15 (IL-15), and methods for modulating immune responses using such viruses. This invention shows that by inserting the human IL-15 gene into the vaccinia genome, more effective vaccines can be generated against infectious agents and cancer. Currently, IL-2 has been approved by the FDA for use in the treatment of patients with metastatic renal cell carcinoma or with metastatic melanoma. It has been used as a component of cancer vaccines and in various approaches for the treatment of AIDS. However, administration of IL-2 is associated with activation-induced cell death (AICD), and may lead to death of T-cells that recognize the antigens expressed in the tumor cells. Thus, IL-15 may be a superior agent in the treatment of cancer, or as a component of a vaccine directed towards cancer or infectious agents. Co-expression of IL-15 with antigens during the immunization process, according to the current invention, leads to induction of CD8+ memory T cells with higher avidity that proliferate more effectively in vivo and persist much longer in the immunized individual in addition to enhancing the levels and persistence of antigen specific antibodies thus providing substantially longer lasting cellular and humoral immunity.
This invention has the potential to be used in a variety of ways, including: (i) an improved, more efficacious vaccine candidate for smallpox, (ii) for incorporation into existing vaccinia based vaccines to enhance and confer superior long lasting immune response to viral and cancer antigens, or (iii) as a valuable source material for IL-15 production, especially should IL-15 be proven as an alternate of more efficacious cytokine than IL-2. More...
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