Divergence in CD8+ T cell epitopes of HIV -1 as an immune escape mechanism

摘要: More than 40 million people are living with human immunodeficiency virus-1 (HIV-1). A prophylactic vaccine inducing a 'sterilizing immunity' is desired to prevent further infections, but will require many years develop. Moreover, vaccines not help the millions of who already infected virus, and face life-long treatment expensive toxic antiretroviral therapy (ART). This dissertation based on proposal that best strategy for these individuals therapeutic attack residual viral reservoirs by expanding HIV-1 specific, primary T cell responses persons's own, autologous virus. Previously, this laboratory demonstrated mature dendritic cells (DC) loaded immunodominant peptides or apoptotic bodies can activate specific memory responses. However, such only partially restored during ART. I hypothesized targeting naive CD8⁺ through DC-based immunotherapy could elicit robust broad response HIV-1. Furthermore, most studies have used consensus strains antigens believe inadequately represent host's diverse pool quasispecies. The current study has provided initial data support be primed in vitro engineered DC, even against representing immune escape variants. therefore supports concept using virus as an antigen demonstrates use sequences expands both vitro. Thus, potential advantage future immunotherapies large repertoire pool. each patient's quasispecies HIV-1, well activation cells, giving broadest control infection Such approach important public health implications having strong positive impact on, improve of, persons It also serves priming model development other infectious agents.