Generating lentiviral vectors for use as a vaccine delivery system
Hood, Alasdair James Murray
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Lentiviruses provide a suitable starting point for the generation of viral vectors for vaccination due to their ability to transduce non-dividing cells, including dendritic cells. This allows the delivery of antigens directly to antigen presenting cells to stimulate an immune response. The most well developed and characterised lentiviral vector is based on HIV-1 which now incorporates safety features to minimise the effects of hazards such as insertional oncogenesis. These HIV-1 vectors have been shown to mediate immunity against several pathogens including: Plasmodium falciparum, the Influenza Virus and Mycobacterium tuberculosis in mouse models. Our group has applied the advances in the HIV-1 system to the visna maedi virus in order to engineer vaccines suitable for sheep. The vaccines will initially be targeted against the sheep pathogens: Teladorsagia circumcinta and Louping Ill Virus; these pathogens have been chosen as current control strategies are insufficient. In this project, antigens previously identified to provide protective immunity, were inserted into the vector cassette of the visna maedi virus system. Expression of these antigens was then shown in a mammalian system by using plasmids to transfect cells in vitro. Vectors encoding these antigens were used to assay expression in cell culture after infection; however, significant expression of antigens was not induced by these vectors. Further development of the vector cassettes is required before they are suitable to be vaccine candidates; however their ability to induce expression of antigens in mammalian cells provides a good basis for future work.