Doherty Institute - Theses
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ItemRecombinant HIV vaccines and mucosal immunity( 2016)More than 36 million people were infected with the human immunodeficiency virus (HIV)-1 in 2015, and 17 million of this population were females. Female HIV infection has wider implications on mother-to-child transmission of HIV and the survival of children in the event of their mother’s death from AIDS. This highlights a critical need for vaccines that prevent female acquisition of HIV infection. In female sexual transmission of HIV, infection of target CD4 T-cells is highly localised in the sub-mucosal cervico-vaginal tissues for several days before systemic dissemination, and displays little or no viral diversity. Cytotoxic CD8 T-lymphocyte (CTL) responses have been correlated with effective control of acute viraemia in HIV-1 infection of humans or simian immunodeficiency virus (SIV) infection in non-human primate model. Elimination of HIV infection by CTL responses is hypothesised to be most effective during this early phase of contained infection in the cervico-vaginal tissue. In this Ph.D. thesis, vaccination strategies for the induction of tissue-resident HIV-specific CTLs in the female reproductive mucosal tissues were investigated. This thesis demonstrated that influenza virus could be genetically engineered to induce intracellular expression of whole HIV-1 p24 capsid protein. The influenza vectors developed were immunogenic for HIV-specific CD8 T-cell responses when used in prime-boost regimens. We exploited the capacity of these recombinant influenza viruses to infect mucosal tissues in order to establish HIV-specific CTL responses in the vagina mucosa. The mucosal vaccination strategies proposed here provide novel approaches for the establishment of frontline vaginal-resident HIV- specific CTLs and may induce heightened local surveillance for protection against vaginal HIV-1 exposure.