Propagation Enhancement of Chimeric Lentiviral Vaccines

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DESCRIPTION (provided by applicant): Propagating chimeric particle vaccines (PCP) are promising candidates for the development of an effective vaccine against HIV, because they have the potential to induce immunity similar to live-attenuated vaccines without the associated safety concerns. Replicating particle-based vaccines will be generated to express lentiviral Gag and Env for the induction of protective neutralizing antibody and cellular immunity against HIV/AIDS. Gag and Env are expressed from a VEE replicon genome and form particles that contain a non-integrating, nonpathogenic, replicating, chimeric VEE/lentiviral genome. However, the propagating chimeric particle does not have a specific mechanism to preferentially package genomic RNA. Currently, the particles produced by the vaccine promiscuously package any available RNA within the cytoplasm of the infected cell. Therefore, the goal of this research is to enhance the specific encapsidation of genomic RNA by Gag/Env PCP, thereby improving the ultimate immunogenicity of the vaccine. The PCP vaccine will be modified to contain alphaviral and lentiviral encapsidation enhancement signals and evaluated for particle formation, specific binding and encapsidation of genomic RNA as well as replication competency.