Immunotherapeutic Strategies for Human Immunodeficiency Virus-1 (HIV-1)
Open AccessThere are approximately 37 million people living with Human Immunodeficiency Virus-1 (HIV-1) worldwide, with less than half, only 17 million people receiving anti-retroviral therapy (ART). ART is unable to cure HIV, allowing latent reservoirs to remain throughout an HIV-infected individuals lifetime. There have been many attempts to develop a cure for HIV, including vaccine and cell therapy based strategies. Elite controllers, a subset of HIV+ individuals, are able to naturally control their infection and have been characterized with having dominant Gag-specific T cell responses. This suggests that elicitation of a strong immune response against HIV may be an effective strategy towards an HIV cure.As such, in this thesis, I explore three immunotherapeutic strategies to target HIV-1: (1) a novel system to identify immunogenic antigens at a mucosal site (Chapter 2), (2) antigen specific T cell therapies derived from seropositive and seronegative donors (Chapters 3-5), and (3) genetic modification to enhance the activity of cell based therapies (Chapter 6). A successful cure strategy for HIV will likely incorporate a combination of approaches including the identification of conserved, immunogenic HIV epitopes, HIV-specific T cell therapies, optimal latency reversing agents that are non-toxic, and genetic modifications to provide HIV resistance, to effectively target the latent HIV reservoir.
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