The long term goal and objective of this research is to use RNA mediated gene delivery as a novel approach to raise rev-independent, anti-HIV-1 gp160 responses. Immunization of gp160 via RNA mediated delivery avoids the complication of rev-dependence, alternate splicing and additional problems associated with genomic integration and long-lived expression, all of which occur in DNA immunization. While some low titer anti-HIV-1 rev responses have been observed in initial experiments with direct intramuscular inoculation of gp160 transcripts, additional work is required to optimize an RNA immunization protocol to improve the titer of the response. In addition, an RNA prime and recombinant subunit boost is proposed to determine the extent and functional character of the immune response. The investigators propose to assess both humoral and cytotoxic T cell responses generated from RNA immunization with full length gp160 transcripts from both the T cell tropic HXB2 isolate and the primary lymphocyte and macrophage tropic isolate ADA.
