Browsing by Subject "Vaccines"
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Item Economic evaluation of using adenovirus type 4 and type 7 vaccines in United States military basic trainees(2014-05) Vazquez, Meredith Hodges; Wilson, James P.Adenoviruses, particularly types 4 and 7, are associated with febrile respiratory illness (FRI) outbreaks in US military basic trainees. Vaccines against these two serotypes controlled FRI in basic trainees until production ceased in the mid-1990s. After contracting a new manufacturer, adenovirus vaccination of military basic trainees resumed in 2011. The purpose of this dissertation was to assess the cost-effectiveness of using the new adenovirus type 4 and type 7 vaccines for the prevention of FRI in US military basic trainees from the perspective of each military branch. Two decision tree models comparing adenovirus vaccination to no adenovirus vaccination were used for this dissertation. The first model is similar to previous models used to assess the cost-effectiveness of the adenovirus vaccine in the military, where the outcome is number of FRI hospitalizations prevented. The second model created for this dissertation used information gathered from published literature and conversations with experts on the adenovirus vaccine. The outcome for the second model was number of training days lost (TDL) averted. Results from part I indicated that adenovirus vaccination of basic trainees was cost-effective as measured by FRI hospitalizations prevented in all US military service branches but the Coast Guard. The model showed that reintroducing the adenovirus vaccine to basic trainees saved the Army $5.8 million, the Navy, $1 million, the Marine Corps, $238,000, and the Air Force, $5.2 million, annually. In addition, adenovirus vaccination prevented 1,221, 543, 317, 677 cases of FRI hospitalization annually in the Army, Navy, Marine Corps, and Air Force respectively. In part II of this study, adenovirus vaccination of basic trainees was the dominant strategy as measured by TDL averted in all US military service branches but the Marine Corps and the Coast Guard. Results indicate that it would cost approximately $37.63 and $563.78 per TDL averted for the Marine Corps and Coast Guard respectively. Both models used for this dissertation provide evidence supporting the cost-effectiveness of using the adenovirus vaccine in US basic trainees in all services but the Coast Guard.Item Evaluation of Vaccines on the Prevalence of Salmonella and/or Campylobacter in Layer and Broiler Chickens(2013-05-22) Garcia, Javier ShalinThe control of foodborne pathogens especially Salmonella and Campylobacter are of great concern to the commercial poultry industry. The control of these pathogens could be essential in the reduction of foodborne illness and deaths related to eggs and poultry meat. Previous studies have found that the presence or disappearance of Salmonella or Campylobacter is linked to various environmental and management-based factors, of which include vaccines used in the industry. Presently, we evaluated the effect of the infectious bronchitis virus (IBV) vaccine on the incidence of Salmonella or Campylobacter prevalence in broiler chicks. In the current study, a high vaccine dosage of IBV vaccine was associated with an increase the prevalence of Campylobacter during the first two weeks of age. Although in a previous study a high vaccine dose of IBV was linked in to increased prevalence of Salmonella, this was not seen in our study. In a subsequent trial, we also evaluated the potential cross-protection against three Salmonella serotypes of two-previously formulated vaccines when used in various dosage combinations. The combination vaccine was effective in reducing shedding of S. Enteritidis however reduction of S. Typhimurium and S. Hadar were not seen consistently. The vaccines were also shown to not significantly affect the body weights of the birds. Vaccines have been an essential component in the control of diseases within flocks in the commercial poultry industry. Ensuring the uniform application of IBV vaccine could help prevent and/or reduce the prevalence of Campylobacter in broiler flocks. The combination vaccine was effective against one serotype of Salmonella but further trials are needed to complete evaluate its potential as a vaccine that could be used in the poultry industry.Item 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. [Keywords: vaccine, novel, peptoid(s), mimetic(s), human immunodeficiency virus (HIV), platform, B cell epitopes, peptide]