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229 Enhancement of Cellular and Humoral Immune Responses to Human Immunodeficiency Virus Type 1 Gag and Pol by a GP-92 Fusion Protein Expressing Highly Immunogenic Gag p17/p24 and Pol p51 Antigens
D. Kmieciak1,2 and D. Kozbor*1
1Temple Univ., Philadelphia, PA, USA and 2Univ. Med. Sci., Poznan, Poland
In this study, we have investigated the immunogenicity of a Gag/Pol fusion protein, designated GP-92, that consists of highly immunogenic regions of human immunodeficiency virus type-1 (HIV-1) Gag (p17 and p24) and Pol (p51) expressed in recombinant vaccinia virus (rVV). The GP-92 construct contains 183 cytotoxic T-lymphocyte (CTL) epitopes with multiple HLA-binding motifs and 49 T-helper (Th) cell epitopes that are encoded by a single, continuous open-reading frame. Immunization studies in the HLA-A2/Kb transgenic mice revealed increased cellular and humoral responses to both gag and pol gene products elicited by the GP-92 construct compared with those induced by a Gag-Pol pseudoparticle-based vaccine. Thus, in addition to a considerable reduction in size compared with the viral Gag-Pol protein, the GP-92 construct is highly immunogenic and may be useful in the development of AIDS vaccines.
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