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Title of Thesis: Induction and Characterization of Immune Responses in Small Animals Using a Venezuelan Equine Encephalitis Virus (VEE) Replicon System, Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Genes Jennifer M. DeVol; Candidate, Masters of Science, 2003 Thesis Directed by: Gerald V. Quinnan, Jr., M.D., Professor and Chair, Department of Preventive Medicine Human immunodeficiency virus type 1 (HIV-1) is the lentivirus responsible for the Acquired Immunodeficiency Syndrome (AIDS) pandemic. Currently, no approved vaccine exists to combat this global human health threat. One approach is to develop a vaccine that induces neutralizing antibodies. To date, the most promising platforms used for induction of neutralizing antibodies against HIV-1 is the Venezuelan equine encephalitis virus (VEE) replicon system. The studies detailed herein have characterized certain aspects of the immune responses induced by the in vivo VEE expression system. Following HIV-1 Env-encoding replicon preparation and immunization of mice, the analysis of those immune responses were carried out using enzyme immunoassays (EIAs) and virus neutralization assays. The data revealed significant anti-HIV-1 Env antibody induction, with intra-clade and to a lesser extent inter-clade neutralizing antibody reactivity. The data obtained from these studies will contribute to the goal of inducing broadly cross-reactive neutralizing antibodies and aid in the development of an effective vaccine for HIV-1.