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129 Effect of Variable Loop Deletion on Envelope Glycoprotein-Specific Cellular Responses and Protection against Challenge with Recombinant Vaccinia Virus Expressing gp160 of Primary HIV-1 Isolates
J. Gzyl*, I. Kiszka, D. Kmieciak, E. Bolesta, T. Naito, and D. Kozbor
Temple Univ., Philadelphia, PA, USA
We have analyzed the effect of a deletion of the hypervariable V3 loop of gp160 (env) on cellular responses and protection against challenge with recombinant vaccinia virus (rVV) expressing gp160 proteins of primary HIV-1 isolates. Immunization studies in the HLA-A2/Kb transgenic mice revealed that the deletion resulted in induction of 3-fold higher CD8+ T-cell responses to a conserved HLA-A2-restricted CTL epitope located in the N-terminal region of gp120 and, to a lesser extent, to an epitope present in the C-terminal region of gp41. The increases in cellular responses to the conserved epitopes of gp160 elicited by the V3 loop-deleted (?V3) env gene products were associated with broader CTL activities. Using rVV-expressing heterologous gp160 proteins in a murine challenge system, we observed that the extent of resistance to viral transmission was higher in animals immunized with the ?V3 than the wild-type (WT) env. Additional studies are in progress using V1/V2- and V1/V2,V3-deleted gp160 to compare the efficacy of each construct in inducing cross-reactive cellular responses and protection against challenge with rVV expressing heterologous env gene products. Results of these experiments suggest that deletion of highly variable sequences may result in generation of env vaccines with an enhanced ability to induce broader cellular responses.
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