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Description
Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines.
ContributorsWang, Shifeng (Author) / Curtiss, Roy (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2015-01-07
Description
Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating antigen-specific antibodies, but in MM the B cells express mutated, non-specific monoclonal antibodies. Therefore, it is hypothesized that antibody-based assay and therapy may be feasible for detecting and treating the disease. In this project, 330k peptide microarrays were used to ascertain the binding affinity of sera antibodies for MM patients with random sequence peptides; these results were then contrasted with normal donor assays to determine the "immunosignatures" for MM. From this data, high-binding peptides with target-specificity (high fluorescent intensity for one patient, low in all other patients and normal donors) were selected for two MM patients. These peptides were narrowed down to two lists of five (10 total peptides) to analyze in a synthetic antibody study. The rationale behind this originates from the idea that antibodies present specific binding sites on either of their branches, thus relating high binding peptides from the arrays to potential binding targets of the monoclonal antibodies. Furthermore, these peptides may be synthesized on a synthetic antibody scaffold with the potential to induce targeted delivery of radioactive or chemotherapeutic molecular tags to only myelomic B cells. If successful, this would provide a novel alternative to current treatments that is less invasive, has fewer side effects, more specifically targets the cause of MM, and reliably diagnoses the cancer in the presymptomatic stage.
ContributorsBerry, Jameson (Co-author) / Buelt, Allison (Co-author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Since its inception in the early 1990s, the concept of gene vaccines, particularly DNA vaccines, has enticed researchers across the board due to its simple design, flexible modification, and overall inexpensive cost of manufacturing. However, the past three decades have proven to be less fruitful than anticipated as scientists have yet to tackle the issue of inducing a strong enough response in humans and non-human primates to protect against foreign pathogens, an issue that has since been coined as the “simian barrier.” This appears to be a human/primate barrier as protective vaccines have been produced for other mammals. Despite millions of dollars in research along with some of the world’s brightest minds chipping in to resolve this, there has yet to be any truly viable solution to overcoming this barrier. With current research illustrating effective applications of RNA vaccines in humans, these studies may be uncovering the solution to the largely unsolved simian barrier dilemma. If vaccines using RNA, the transcribed version of DNA, are effective in humans, the problem may be inefficient transcription of the DNA. This may be attributable to a DNA promoter that has insufficient activity in primates. Additionally, with DNA vaccines being even cheaper and easier to manufacture than RNA vaccines, along with having no required cold chain for distribution, this concept remains more promising than RNA vaccines that are further along in clinical trials.
ContributorsWillis, Joshua Aaron (Author) / Johnston, Stephen (Thesis director) / Sykes, Kathryn (Committee member) / Shen, Luhui (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
Description
The purpose of my honors thesis project was to generate the tools needed for in vivo imaging by determining the optimal plasmid-fluorophore combination. To determine the optimal plasmid and fluorophore, asd plasmids were constructed with various promoters, origins of replications, and red fluorophores. The optimal asd plasmid for fluorescent in vivo imaging was determined by the plasmid stability, growth rate, and growth phase dependence on fluorescent intensity. The end goal is to be able to use the asd plasmid in vaccine strains for the purpose of in vivo imaging of the recombinant attenuated Salmonella vaccine (RASV).
ContributorsEudy, L. Adam (Author) / Curtiss, Roy (Thesis director) / Roland, Kenneth (Committee member) / Forbes, Stephen (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12