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Vaccines are modern medicine’s best way of combating the majority of viral and bacterial illnesses and contagions to date. Thanks to the introduction of vaccines since the first uses of them in 1796 (Jenner’s smallpox vaccine), they have drastically reduced figures of disease worldwide, turning once lethal and life changing

Vaccines are modern medicine’s best way of combating the majority of viral and bacterial illnesses and contagions to date. Thanks to the introduction of vaccines since the first uses of them in 1796 (Jenner’s smallpox vaccine), they have drastically reduced figures of disease worldwide, turning once lethal and life changing conditions into minor annoyances; Some of these afflictions have even become nonexistent or even extinct in certain parts of the world outside of a controlled laboratory setting. With many advancements and overwhelming evidence proving their efficiency, it is clear that vaccines have become nothing less than a necessity for everyday healthcare in today’s world. <br/>The greatest contributor to the creation and evolution of vaccines throughout the years is by far the progress and work done in the field of molecular and cellular biology. These advancements have become the bedrock of modern vaccination, as shown by the differing types of vaccines and their methodology. The most common varieties of vaccines are include ‘dead’ or inactivated vaccines, one such example being the pertussis strain of vaccines, which have either dead or torn apart cells for the body to easily fight off, allowing the immune system to easily and quickly counter the illness; Additionally, there are also live attenuated vaccines (LAVs) in which a weaker version of the pathogen is introduced to the body to stimulate an immune response, or a recombinant mRNA vaccine where mRNA containing the coding for an antigen is presented for immunological response, the latter being what the current COVID-19 vaccines are based on. This is in part aided by the presence of immunological adjuvants, antigens and substances that the immune system can recognize, target, and remember for future infections. However, for more serious illnesses the body needs a bigger threat to analyze, which leads to live vaccines- instead of dead or individual components of a potential pathogen, a weakened version is created in the lab to allow the body to combat it. The idea behind this is the same, but to a larger degree so a more serious illness such as measles, mumps, and rubella (MMR) do not infect us.<br/>However, for the past couple of decades the public’s views on vaccination has greatly varied, with the rise of fear and disinformation leading those to believe that modern medicine is a threat in disguise. The largest of these arguments began in the late 90’s, when Dr. Andrew Wakefield published an article under the Lancet with false information connecting vaccinations to the occurrence of autism in younger children- a theory which has since then been proven incorrect numerous times over. Unfortunately, the rise of hysteria and paranoia in people, along with more misinformation from misleading sources, have strengthened the anti-vaccination cause and has made it into a serious threat to the health of those world-wide.<br/>The aim of this thesis is to provide an accurate and thorough analysis on these three themes- the history of vaccines, their inner workings and machinations in providing immune defenses for the body, and the current controversy of the anti-vaccination movement. Additionally, there will be two other sections going in-depth on two specific areas where vaccination is highly important; The spread and fear of the Human Immunodeficiency Virus (HIV) has been around for nearly four decades, so it begs the question: what makes this such a difficult virus, and how can a vaccine be created to combat it? Additionally, in the last year the world has encountered a new virus that has evolved into a global pandemic, SARS-COV 2. This new strain of coronavirus has shown itself to be highly contagious and rapidly mutating, and the race to quickly develop a vaccine to counteract it has been on-going since its first major infections in Wuhan, China. Overall, this thesis will go in-depth in providing the most accurate, up-to-date, and critical information regarding vaccinations today.

ContributorsKolb Celaya, Connor Emilio (Author) / Topal, Emel (Thesis director) / Huffman, Holly (Committee member) / College of Integrative Sciences and Arts (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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White-nose syndrome (WNS) is a fungal infection devastating bat populations throughout eastern North America. WNS is caused by a fungus, Pseudogymnoascus destructans (Pd), that invades the skin of hibernating bats. While there are a number of treatments being researched, there is currently no effective treatment for WNS that is deployed

White-nose syndrome (WNS) is a fungal infection devastating bat populations throughout eastern North America. WNS is caused by a fungus, Pseudogymnoascus destructans (Pd), that invades the skin of hibernating bats. While there are a number of treatments being researched, there is currently no effective treatment for WNS that is deployed in the field, except a few being tested on a limited scale. Bats have lowered immune function and response during hibernation, which may increase susceptibility to infection during the winter months. Antimicrobial peptides (AMPs) are a crucial component of the innate immune system and serve as barriers against infection. AMPs are constitutively expressed on skin and facilitate wound healing, stimulate other immune responses, and may also stay active on bat skin during hibernation. AMPs are expressed by all tissues, have direct killing abilities against microbes, and are a potential treatment for bats infected with Pd. In this investigation, the fungicidal activity of several readily available commercial AMPs were compared, and killing assay protocols previously investigated by Frasier and Lake were replicated to establish a control trial for use in future killing assays. Another aim of this investigation was to synthesize a bat-derived AMP for use in the killing assay. Sequences of bat-derived AMPs have been identified in bat skin samples obtained from a large geographic sampling of susceptible and resistant species. Contact was made with GenScript Inc., the company from which commercially available AMPs were purchased, to determine the characteristics of peptide sequences needed to synthesize an AMP for lab use. Based on recommendations from GenScript Inc., peptide sequences need to have a hydrophobicity of less than 50% and a sequence length of less than 50 amino acids. These criteria serve as a potential barrier because none of the known bat-derived sequences analyzed satisfy both of these requirements. The final aim of this study was to generate a conceptual model of the immune response molecules activated when bats are exposed to a fungal pathogen such as Pd. Overall, this work investigated sources of variability between trials of the killing assay, analyzed known bat-derived peptide sequences, and generated a conceptual model that will serve as a guideline for identification of immune response molecules on the skin of bats in future proteomics work.
ContributorsBarton, Madisen L (Author) / Moore, Marianne (Thesis director) / Penton, Christopher (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Phytohemagglutinin (PHA) is a plant lectin commonly used to stimulate and test responses of the immune system and is known to induce T cell proliferation, agglutinate human leukocytes, and yield adjustments in lymphocyte populations. What is not well know is how responses to PHA correlate with a host's ability to

Phytohemagglutinin (PHA) is a plant lectin commonly used to stimulate and test responses of the immune system and is known to induce T cell proliferation, agglutinate human leukocytes, and yield adjustments in lymphocyte populations. What is not well know is how responses to PHA correlate with a host's ability to resist or recover from pathogen invasion. This study uses information from previously published studies to determine whether or not PHA can be a good indicator of disease severity or disease resistance in a host. With PHA having the abilities that it does, immune responses to PHA may correlate with responses important for pathogen resistance and clearance. Such a relationship could only be uncovered if in vivo or in vitro responses to PHA are measured and, independent from the PHA challenge, symptoms and/or mortality rates of hosts are documented after pathogen exposure. An in vitro response can be detected by measuring cellular proliferation in response to PHA followed by separate cell cultures exposed to a pathogen. While an in vivo response can be detected by measuring variation in swelling in response to an injection of PHA. In reviewing a broad range of articles that meet my criteria, the majority of articles failed to show a strong relationship between PHA and disease severity or disease resistance. Therefore, immunologists must consider the usefulness of the PHA tests as a measure of immunocompetence, which is a host's ability to predict response to a pathogen. According to the literature, using PHA does not predict responses to pathogen invasion. However, it is possible that with carefully designed experiments, it could be determined that PHA does provide an indication of pathogen resistance in certain host species exposed to specific pathogen.
ContributorsMackey, Tracy Michelle (Author) / Moore, Marianne (Thesis director) / Penton, Ryan (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, declared in March 2020 resulted in an unprecedented scientific effort that led to the deployment in less than a year of several vaccines to prevent severe disease, hospitalizations, and death from coronavirus disease 2019 (COVID-19). Most vaccine models focus on the

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, declared in March 2020 resulted in an unprecedented scientific effort that led to the deployment in less than a year of several vaccines to prevent severe disease, hospitalizations, and death from coronavirus disease 2019 (COVID-19). Most vaccine models focus on the production of neutralizing antibodies against the spike (S) to prevent infection. As the virus evolves, new variants emerge that evade neutralizing antibodies produced by natural infection and vaccination, while memory T cell responses are long-lasting and resilient to most of the changes found in variants of concern (VOC). Several lines of evidence support the study of T cell-mediated immunity in SARS-CoV-2 infections. First, T cell reactivity against SARS-CoV-2 is found in both (cluster of differentiation) CD4+ and CD8+ T cell compartments in asymptomatic, mild, and severe recovered COVID-19 patients. Second, an early and stronger CD8+ T cell response correlates with less severe COVID-19 disease [1-4]. Third, both CD4+ and CD8+ T cells that are reactive to SARS-CoV-2 viral antigens are found in healthy unexposed individuals suggesting that cross-reactive and conserved epitopes may be protective against infection. The current study is focused on the T cell-mediated response, with special attention to conserved, non-spike-cross-reactive epitopes that may be protective against SARS-CoV-2. The first chapter reviews the importance of epitope prediction in understanding the T cell-mediated responses to a pathogen. The second chapter centers on the validation of SARS-CoV-2 CD8+ T cell predicted peptides to find conserved, immunodominant, and immunoprevalent epitopes that can be incorporated into the next generation of vaccines against severe COVID-19 disease. The third chapter explores pre-existing immunity to SARS-CoV-2 in a pre-pandemic cohort and finds two highly immunogenic epitopes that are conserved among human common cold coronaviruses (HCoVs). To end, the fourth chapter explores the concept of T cell receptor (TCR) cross-reactivity by isolating SARS-CoV-2-reactive TCRs to elucidate the mechanisms of cross-reactivity to SARS-CoV-2 and other human coronaviruses (HCoVs).
ContributorsCarmona, Jacqueline (Author) / Anderson, Karen S (Thesis advisor) / Lake, Douglas (Thesis advisor) / Maley, Carlo (Committee member) / Mangone, Marco (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2023
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Type 1 diabetes (T1D) is the result of an autoimmune attack against the insulin-producing β-cells of the pancreas causing hyperglycemia and requiring the individual to rely on life-long exogenous insulin. With the age of onset typically occurring in childhood, there is increased physical and emotional stress to the child as

Type 1 diabetes (T1D) is the result of an autoimmune attack against the insulin-producing β-cells of the pancreas causing hyperglycemia and requiring the individual to rely on life-long exogenous insulin. With the age of onset typically occurring in childhood, there is increased physical and emotional stress to the child as well as caregivers to maintain appropriate glucose levels. The majority of T1D patients have antibodies to one or more antigens: insulin, IA-2, GAD65, and ZnT8. Although antibodies are detectable years before symptoms occur, the initiating factors and mechanisms of progression towards β-cell destruction are still not known. The search for new autoantibodies to elucidate the autoimmune process in diabetes has been slow, with proteome level screenings on native proteins only finding a few minor antigens. Post-translational modifications (PTM)—chemical changes that occur to the protein after translation is complete—are an unexplored way a self-protein could become immunogenic. This dissertation presents the first large sale screening of autoantibodies in T1D to nitrated proteins. The Contra Capture Protein Array (CCPA) allowed for fresh expression of hundreds of proteins that were captured on a secondary slide by tag-specific ligand and subsequent modification with peroxynitrite. The IgG and IgM humoral response of 48 newly diagnosed T1D subjects and 48 age-matched controls were screened against 1632 proteins highly or specifically expressed in pancreatic cells. Top targets at 95% specificity were confirmed with the same serum samples using rapid antigenic protein in situ display enzyme-linked immunosorbent assay (RAPID ELISA) a modified sandwich ELISA employing the same cell-free expression as the CCPA. For validation, 8 IgG and 5 IgM targets were evaluated with an independent serum sample set of 94 T1D subjects and 94 controls. The two best candidates at 90% specificity were estrogen receptor 1 (ESR1) and phosphatidylinositol 4-kinase type 2 beta (PI4K2B) which had sensitivities of 22% (p=.014) and 25% (p=.045), respectively. Receiver operating characteristic (ROC) analyses found an area under curve (AUC) of 0.6 for ESR1 and 0.58 for PI4K2B. These studies demonstrate the ability and value for high-throughput autoantibody screening to modified antigens and the frequency of Type 1 diabetes.
ContributorsHesterman, Jennifer (Author) / LaBaer, Joshua (Thesis advisor) / Borges, Chad (Committee member) / Sweazea, Karen (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022