Browsing by Subject "Vaccines"
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Item New Approaches to the Development of Peptoid Vaccines(2015-04-07) Desmond, Angela; Pfeiffer, Julie K.; Vitetta, Ellen S.; Levine, Beth; Niederkorn, Jerry Y.; Ward, E. SallyThe ideal prophylactic vaccine against a toxin or pathogen should elicit the production of broadly protective antibodies against conserved epitopes. However, the epitopes that elicit these antibodies are often not immunodominant and even when they are, characterizing and synthesizing them can be difficult, particularly if they are conformational. The long-term goal of this work was to develop prophylactic vaccines that elicit such antibodies without epitope characterization. To develop such a vaccine platform, it was hypothesized that screening large one-bead-one-compound libraries of synthetic compounds with monoclonal antibodies that have already been shown to be broadly protective against a toxin or pathogen would allow the identification of mimetic B cell epitopes. For this platform, peptoids were chosen to construct one-bead-one-compound libraries. Peptoids are N-oligosubstituted glycines that resemble peptides but bear their side groups on backbone nitrogens instead of carbons. This renders them protease resistant and enormously diverse, since they are not restricted to the twenty standard amino acids. Furthermore, previous work had demonstrated that a monoclonal antibody could be used to screen libraries of peptoids. Moreover, while peptoids themselves were not immunogenic, the attachment of peptoids to carrier proteins using a linker elicited antibodies against the peptoid/linker. Such T-cell dependent antigens elicited high-affinity, class-switched antibodies. The goal of this dissertation research was to continue optimizing the magnetic and color-based assays by which peptoid vaccine candidates could be identified and to screen libraries with neutralizing monoclonal antibodies against West Nile virus and murine norovirus type 1. In addition, the immunogenicity of peptoids was further examined by designing a peptoid-carrier, using it to immunize rabbits, and demonstrating that anti-peptoid antibodies could be affinity-purified from the resulting antisera. This antibody was then used in further optimization of the magnetic screening assay to ensure that future screens will efficiently and specifically identify the best vaccine candidates.Item [News](1981-09-18) Rutherford, SusanItem A Novel Platform to Generate Synthetic Vaccine Candidates(2012-07-10) Case, Allison Carroll; Vitetta, Ellen S.Vaccination remains the optimal means to prevent infectious disease by inducing antibodies that confer protective immunity against the pathogen in question [1-3]. However, there remain viruses against which no effective vaccines exists including human immunodeficiency virus (HIV), West Nile Virus (WNV) and hepatitis C virus (HCV). These viruses and others evade the immune response by undergoing rapid mutations in immunodominant epitopes [4-6]. In addition, although they usually express conserved epitopes that are important for inducing neutralizing antibodies, in many cases these are not immunodominant. Traditional techniques in vaccine development have not been able to overcome these barriers for these and other viruses. Subunit and peptide vaccines are very safe but it is often difficult to identify the key epitopes needed to make them effective. New approaches to developing safe vaccines that induce broadly neutralizing antibodies are needed. Therefore, the long term goal of this project was to generate vaccine candidates for any virus for which a neutralizing antibody existed or could be made without prior knowledge of the protective epitope(s). Furthermore, we desired a way to administer these vaccine candidates safely and before exposure so as to induce neutralizing antibodies. To accomplish these goals, we began with the development of a platform to generate synthetic vaccine candidates. This platform consisted of 1) libraries of B cell epitopes or “shapes” prepared by displaying peptoid sequences on beads, 2) neutralizing monoclonal antibodies (MAbs) to select the peptoids that bound to the antibody’s antigen-combining site, and 3) protein G dynabeads (PGDs) and a magnet to bind and isolate antibody bound peptoid beads. Any sequences identified in the platform as potential B cell mimetics were further evaluated in two validation assays. The first consisted of a “color screening” assay to determine that the isolated on-bead peptoids were bound by antibody. The second confirmed that these peptoids would fail to be bound by antibody if an excess of the native antigen was added (i.e. that peptoid sequences were bound by the antibody’s binding sites). The major accomplishments to emerge from this study were 1) the creation of an optimized magnetic screening platform for the isolation of peptide B cell epitopes from an on-bead library, 2) a magnetic screening platform optimized for the isolation of peptoid B cell epitopes from a peptoid library, and 3) the identification of potential peptoid B cell epitope mimetics of FLAG peptide from a peptoid library using a MAb. Taken together, a sensitive, specific, and reproducible platform to identify vaccine candidates from a peptoid library was created. This platform is particularly important for viruses like HIV, HCV, and WNV where mutation makes foreknowledge of conserved, neutralizing epitopes difficult. Once sufficiently large and diverse libraries are created, the B cell epitope mimetics (vaccine candidates) identifiable by this platform will have several advantages over their peptide counterparts. These peptoid-based vaccines are “safe” as there is no potential for reversion, they are less expensive and faster to synthesize than peptides, they are not dependent on the twenty amino acids, and the B cell epitopes identified with this platform can be conjugated to carrier in such a way that the multivalency and immunodominance can be controlled making this platform advantageous both to the generation of new vaccine candidates and in reformulating current vaccines.Item [Southwestern News](2004-11-30) Siegfried, Amanda; Maier, ScottItem [Southwestern News](2002-02-04) Carter, WayneItem [Southwestern News](2002-09-04) Carter, WayneItem [Southwestern News](2004-12-13) Morales, KatherineItem [Southwestern News](2004-08-12) Siem, Staishy BostickItem [Southwestern News](2002-03-09) Carter, WayneItem [Southwestern News](2001-12-28) Echeverria, IoneItem [UT Southwestern Medical Center News](2010-09-10) Shear, Kristen HollandItem [UT Southwestern Medical Center News](2010-10-12) McKenzie, AlineItem [UT Southwestern Medical Center News](2011-06-28) Russell, RobinItem [UT Southwestern Medical Center News](2008-03-25) McKenzie, AlineItem Vaccine hesitancy(2021-05-21) DuVal, TaraItem Viral hepatitis: recent developments(1981-08-27) Shorey, J. W.