Evaluation of the Efficacy of a Novel DNA Vaccine Against Toxoplasma gondii
Advisor Information
Dr. Paul Davis
Location
Room 249
Presentation Type
Oral Presentation
Start Date
1-3-2019 2:15 PM
End Date
1-3-2019 3:15 PM
Abstract
Toxoplasma gondii is an obligate intracellular parasite that has the ability to infect all nucleated mammalian cells and is found worldwide. This protozoan parasite can cause severe ocular and neurological disease in immunocompromised persons and fetuses. While there are treatments available for individuals infected with the tachyzoite stage of the parasite, which defines the acute infection, there is no effective way to treat for the latent cyst forming stage which is associated with behavioral changes. Thus, there is a need for an effective protective vaccine. This work highlights the design of a versatile DNA sequence that will function in conjunction with a novel delivery system that seeks to stimulate T cell- and antibody-mediated memory responses at mucosal pathogen entry sites, as well as outlining the current and future experiments that must be completed to show the vaccines efficacy against infection. As multi-epitope DNA vaccines have been shown to provide effective protection against other pathogens, the developed sequence consists of three full length T. gondii genes, GRA7, SAG1, and MIC1 separated by tri-alanine linkers. The sequence is designed in such a way that the latter two genes are easily removed, allowing for observations of effects due to plasmid size. Also included in the vaccine design are a universal CD4+ T cell epitope (PADRE), a decapeptide derived from T. gondii gene GRA6 that has shown to produce an immunodominant and protective response (HF10), and CpG oligodeoxynucleotides that serve as a toll-like receptor agonist adjuvant. This design provides the optimal sequence for testing a DNA vaccine with a novel delivery system against T. gondii. Experiments to be conducted include vaccine transfection into mammalian cells to confirm the ability of the protein to be expressed, enzyme-linked immunosorbent assays to display the capability of the vaccine to elicit both a humoral and cell mediated immune response, and a demonstration of the vaccines capacity to provide effective protection against infection in vivo.
Evaluation of the Efficacy of a Novel DNA Vaccine Against Toxoplasma gondii
Room 249
Toxoplasma gondii is an obligate intracellular parasite that has the ability to infect all nucleated mammalian cells and is found worldwide. This protozoan parasite can cause severe ocular and neurological disease in immunocompromised persons and fetuses. While there are treatments available for individuals infected with the tachyzoite stage of the parasite, which defines the acute infection, there is no effective way to treat for the latent cyst forming stage which is associated with behavioral changes. Thus, there is a need for an effective protective vaccine. This work highlights the design of a versatile DNA sequence that will function in conjunction with a novel delivery system that seeks to stimulate T cell- and antibody-mediated memory responses at mucosal pathogen entry sites, as well as outlining the current and future experiments that must be completed to show the vaccines efficacy against infection. As multi-epitope DNA vaccines have been shown to provide effective protection against other pathogens, the developed sequence consists of three full length T. gondii genes, GRA7, SAG1, and MIC1 separated by tri-alanine linkers. The sequence is designed in such a way that the latter two genes are easily removed, allowing for observations of effects due to plasmid size. Also included in the vaccine design are a universal CD4+ T cell epitope (PADRE), a decapeptide derived from T. gondii gene GRA6 that has shown to produce an immunodominant and protective response (HF10), and CpG oligodeoxynucleotides that serve as a toll-like receptor agonist adjuvant. This design provides the optimal sequence for testing a DNA vaccine with a novel delivery system against T. gondii. Experiments to be conducted include vaccine transfection into mammalian cells to confirm the ability of the protein to be expressed, enzyme-linked immunosorbent assays to display the capability of the vaccine to elicit both a humoral and cell mediated immune response, and a demonstration of the vaccines capacity to provide effective protection against infection in vivo.