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  • Title: Enhancement of cellular and humoral immune responses to human immunodeficiency virus type 1 Gag and Pol by a G/P-92 fusion protein expressing highly immunogenic Gag p17/p24 and Pol p51 antigens.
    Author: Kmieciak D, Bolesta E, Naito T, Gzyl J, Kaneko Y, Kozbor D.
    Journal: J Hum Virol; 2001; 4(6):306-16. PubMed ID: 12082397.
    Abstract:
    OBJECTIVES: Immunity to the human immunodeficiency virus type-1 (HIV-1) G/P-92 fusion protein consisting of highly immunogenic regions of Gag (p17 and p24) and Pol (p51) expressed in recombinant vaccinia virus (vG/P-92) was compared with responses to the entire viral Gag-Pol precursor protein (vVK1). STUDY DESIGN/METHODS: We analyzed the level of Gag and Pol protein expression in vG/P-92-infected cells as well as the ability of the G/P-92 fusion protein to form virus-like particles (VLP) in infected cultures. The efficacy of vG/P-92 and vVK1 vaccines was evaluated in a murine model by measuring T helper (Th), cytotoxic T lymphocyte (CTL), and antibody responses to Gag and Pol antigens. RESULTS: The deletion of a frameshift site resulted in an increased level of Pol in cells expressing the G/P-92 fusion protein. Particles budding from the plasma membrane were detected in both vG/P-92- and vVK1-infected cells, but the release of VLP was less efficient from cells expressing the G/P-92 fusion protein than the entire gag-pol gene product. Immunization with vG/P-92 vector elicited a higher level of cellular and humoral responses to both Gag and Pol antigens than the vVK1 vaccine. CONCLUSIONS: The enhanced immunogenicity of the G/P-92 fusion protein compared with the entire viral gag-pol gene product might be related to a higher intracellular level of Pol and Gag expression due to the deletion of a frameshift site and less efficient transport of VLP from vG/P-92-infected cells, respectively.
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