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Description
The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need to understand vaccination from vaccine design to prediction of vaccine efficacy using mathematical models. Post-exposure vaccination with VACV has been suggested to be effective if administered within four days of smallpox exposure although this has not been definitively studied in humans. The first and second chapters analyze post-exposure prophylaxis of VACV in an animal model using v50ΔB13RMγ, a recombinant VACV expressing murine interferon gamma (IFN-γ) also known as type II IFN. While untreated animals infected with wild type VACV die by 10 days post-infection (dpi), animals treated with v50ΔB13RMγ 1 dpi had decreased morbidity and 100% survival. Despite these differences, the viral load was similar in both groups suggesting that v50ΔB13RMγ acts as an immunoregulator rather than as an antiviral. One of the main characteristics of VACV is its resistance to type I IFN, an effect primarily mediated by the E3L protein, which has a Z-DNA binding domain and a double-stranded RNA (dsRNA) binding domain. In the third chapter a VACV that independently expresses both domains of E3L was engineered and compared to wild type in cells in culture. The dual expression virus was unable to replicate in the JC murine cell line where both domains are needed together for replication. Moreover, phosphorylation of the dsRNA dependent protein kinase (PKR) was observed at late times post-infection which indicates that both domains need to be linked together in order to block the IFN response. Because smallpox has already been eradicated, the utility of mathematical modeling as a tool for predicting disease spread and vaccine efficacy was explored in the last chapter using dengue as a disease model. Current modeling approaches were reviewed and the 2000-2001 dengue outbreak in a Peruvian region was analyzed. This last section highlights the importance of interdisciplinary collaboration and how it benefits research on infectious diseases.
ContributorsHolechek, Susan A (Author) / Jacobs, Bertram L (Thesis advisor) / Castillo-Chavez, Carlos (Committee member) / Frasch, Wayne (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
Description
Plants are a promising upcoming platform for production of vaccine components and other desirable pharmaceutical proteins that can only, at present, be made in living systems. The unique soil microbe Agrobacterium tumefaciens can transfer DNA to plants very efficiently, essentially turning plants into factories capable of producing virtually any gene. While genetically modified bacteria have historically been used for producing useful biopharmaceuticals like human insulin, plants can assemble much more complicated proteins, like human antibodies, that bacterial systems cannot. As plants do not harbor human pathogens, they are also safer alternatives than animal cell cultures. Additionally, plants can be grown very cheaply, in massive quantities.
In my research, I have studied the genetic mechanisms that underlie gene expression, in order to improve plant-based biopharmaceutical production. To do this, inspiration was drawn from naturally-occurring gene regulatory mechanisms, especially those from plant viruses, which have evolved mechanisms to co-opt the plant cellular machinery to produce high levels of viral proteins. By testing, modifying, and combining genetic elements from diverse sources, an optimized expression system has been developed that allows very rapid production of vaccine components, monoclonal antibodies, and other biopharmaceuticals. To improve target gene expression while maintaining the health and function of the plants, I identified, studied, and modified 5’ untranslated regions, combined gene terminators, and a nuclear matrix attachment region. The replication mechanisms of a plant geminivirus were also studied, which lead to additional strategies to produce more toxic biopharmaceutical proteins. Finally, the mechanisms employed by a geminivirus to spread between cells were investigated. It was demonstrated that these movement mechanisms can be functionally transplanted into a separate genus of geminivirus, allowing modified virus-based gene expression vectors to be spread between neighboring plant cells. Additionally, my work helps shed light on the basic genetic mechanisms employed by all living organisms to control gene expression.
In my research, I have studied the genetic mechanisms that underlie gene expression, in order to improve plant-based biopharmaceutical production. To do this, inspiration was drawn from naturally-occurring gene regulatory mechanisms, especially those from plant viruses, which have evolved mechanisms to co-opt the plant cellular machinery to produce high levels of viral proteins. By testing, modifying, and combining genetic elements from diverse sources, an optimized expression system has been developed that allows very rapid production of vaccine components, monoclonal antibodies, and other biopharmaceuticals. To improve target gene expression while maintaining the health and function of the plants, I identified, studied, and modified 5’ untranslated regions, combined gene terminators, and a nuclear matrix attachment region. The replication mechanisms of a plant geminivirus were also studied, which lead to additional strategies to produce more toxic biopharmaceutical proteins. Finally, the mechanisms employed by a geminivirus to spread between cells were investigated. It was demonstrated that these movement mechanisms can be functionally transplanted into a separate genus of geminivirus, allowing modified virus-based gene expression vectors to be spread between neighboring plant cells. Additionally, my work helps shed light on the basic genetic mechanisms employed by all living organisms to control gene expression.
ContributorsDiamos, Andy (Author) / Mason, Hugh S (Thesis advisor) / Mor, Tsafrir (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2017
Description
Limited research has analyzed how culture might influence the utilization of social support. To address this deficiency, the present study investigated preferences for social support among East-Asian, Hispanic, and White participants. In this set of studies, a comprehensive social support taxonomy was constructed in order to better identify and conceptualize the various support subtypes found in the literature. Based on the taxonomy, a questionnaire measure for preferences of different types of social support was developed. Participants were asked to rate how helpful they would find each supportive action made by a friend or family member on a seven-point Likert scale. Based on the responses of 516 Amazon Mechanical Turk workers, a five-factor solution for an 18-item scale emerged from a factor analysis. The social support subscales supported by the factor analysis were emotional, tangible, self-referencing, reappraisal, and distraction. The questionnaire was used to assess similarities and differences among East-Asian, Hispanic, and White participants in terms of preferences for providing and receiving social support. Based on the results of 299 college-age students, an analysis of variance on individually standardized ("ipsatized") responses was conducted in order to eliminate the positioning effect of culture. A main effect of ethnicity (p=.05) and an interaction between ethnicity and sex (p=.02) were significant for the preference of tangible social support. A main effect of ethnicity (p=.04) and an interaction between ethnicity and sex (p=.05) were significant for the preference of reappraisal social support. Clinical implications of our research findings are discussed.
ContributorsCampagna, Allegra Xiu Hong (Author) / Shiota, Michelle N. (Thesis director) / Campos, Belinda (Committee member) / Yee, Claire (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The purpose of this thesis is to explore if any correlation exists between the proposed components of happiness with overall self-perceived happiness. This thesis also explores how introversion and extraversion, gender, and working status affects the proposed components of happiness for college students and how their happiness influences engagement, motivation, preference of organizational culture, and the activities that they engage in. This research was gathered from secondary sources and a survey that was given to undergraduate students at Arizona State University. We found that well-being, gratitude, achievement, psychological empowerment, and affection contribute to both extraverts and introverts' happiness. In addition, we found that extraverts reported higher means than introverts in each factor; including happiness in general and what contributes to it. Contrary to popular belief, our research shows that autonomy either had no correlation or negatively correlates with happiness. In addition, we found that both extraverts and introverts participate in social and nonsocial activities rather than solely on their expected type of activity. Our research also shows that females reported higher means than males on gratitude, achievement, and autonomy. One significant implication of this study is that it can help individuals to better understand themselves and people they interact with.
ContributorsVasquez, Delia (Co-author) / Lopez, Miguel (Co-author) / LePine, Marcie (Thesis director) / Arce, Alma (Committee member) / Barrett, The Honors College (Contributor) / Department of Supply Chain Management (Contributor) / Department of Psychology (Contributor) / School of Accountancy (Contributor)
Created2014-12
Description
This paper explains what factors influence mental health issues and what type of care is provided in various countries. The countries in this study will include the United States, Japan, Ethiopia and South Africa, all of which have varying degrees of ethnic diversity, economic status and understanding of mental health issues. It discusses the specific healthcare systems in each country, as well as the attitudes and problems associated with depression and schizophrenia, two prevalent mental health disorders. This paper examines the different ways that a diagnosis is reached for schizophrenia and major depression in these different countries, as well as what methods are used for treating individuals with these disorders. It will also examine the prominent notion that schizophrenia has better outcomes in developing countries than in places that have wider medical care available. It then discusses what treatments are available in each country, as well as social constructs that exist regarding those treatments in order to understand the ways that treatments can be expanded to improve outcomes. This paper will then examine the different outcomes of these mental health disorders that are common in each country, and conclude with ideas on how to make global mental health a reality.
ContributorsOlsen, Rachel Lindsay (Author) / Gaughan, Monica (Thesis director) / Wood, Reed (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Human Evolution and Social Change (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh (Thesis director) / Mor, Tsafrir (Committee member) / Diamos, Andrew (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Vaccine opposition is a growing problem in developed countries where dropping vaccination rates threaten general public health by laying the foundation for resurgence and reemergence of previously eradicated infectious diseases. This thesis argues that the current movement is only the most recent incarnation of opposition that has co-evolved with vaccine practices for the duration of their mutual histories. Part one provides a historical context for the current movement using the example of the development and deployment of the smallpox vaccine as a representative timeline of vaccine acceptance and opposition. Part two describes the current movement in the United States and the United Kingdom, interprets the reasons for the conclusions drawn by vaccine-concerned parents, and provides a framework for public health officials to approach the issues.
ContributorsKost, Stephanie Michelle (Author) / Lynch, John (Thesis director) / Hurlbut, Ben (Committee member) / Robert, Jason (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2013-12
Description
Dengue virus infects millions of people every year. Yet there is still no vaccine available to prevent it. Here we use a neutralizing epitope determinant on the dengue envelope (E) protein as an immunogen to be vectored by a measles virus (MV) vaccine. However the domain III (DIII) of the dengue 2 E protein is too small to be immunogenic by itself. In order for it to be displayed on a larger particle, it was inserted into the amino terminus of small hepatitis B surface antigen (HBsAg, S) coding sequence. To generate the recombinant MV vector and verify the efficiency of this concept, a reverse genetics system was used where the MV vectors express one or two additional transcription units to direct the assembly of hybrid HBsAg particles. Two types of recombinant measles virus were produced: pB(+)MVvac2(DIII-S,S)P and pB(+)MVvac2(DIII-S)N. Virus recovered from pB(+)MVvac2(DIII-S,S)P was viable. An ELISA assay was performed to demonstrate the expression and secretion of HBsAg. Supernatant from MVvac2(DIII-S,S)P infected cells confirmed that hybrid HBsAg-domain III particles with a density similar to traditional HBsAg particles were released. Characteristics of the subviral particle have been analyzed for the successful incorporation of domain III. The replication fitness of the recombinant MV was evaluated using multi-step growth kinetics and showed reduced replication fitness when compared to the parental strain MVvac2. This demonstrates that viral replication is hindered by the addition of the two inserts into MV genome. Further analysis of MVvac2(DIII-S)N is needed to justify immune response studies in a small animal model using both of the generated recombinant vectors.
ContributorsHarahap, Indira Saridewi (Author) / Reyes del Valle, Jorge (Thesis director) / Hogue, Brenda (Committee member) / Misra, Rajeev (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
As the daughter of Mexican parents, I was raised with family-centered values which conflict with the values of independence, freedom and individuality stressed in the United States. Being a minority has become part of my identity, thus influencing how I make decisions about finances and traveling. Minorities are faced with many more concern, like familial concerns and financial obligations which hinder their desire to attempt to travel (Salisbury, Paulsen, & Ernest, 2011). My main concerns were convincing my parents that traveling to Nicaragua and studying abroad in Greece and Italy would be beneficial to my college experience, along with financially being able to go through with each experience. The main purpose of my thesis is to share what it is like to be a minority faced with cultural and financial obstacles that make it difficult to travel and how the experience is shaped due to these obstacles.
ContributorsValtierra, Nancy Jazmin (Author) / Larson, Elizabeth (Thesis director) / Facinelli, Diane (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / Graduate College (Contributor)
Created2014-05
Description
Abstract Development of a Vaccine for Immunization Against Smallpox and Anthrax Jason Maurice Cameron Biological weapons are often considered to be the most dangerous weapons of mass destruction because of there potential to infect huge numbers of people, who may then in turn infect others who were not even present at the point of initial impact. Among the most feared biological weapons are those that contain smallpox and anthrax because of these diseases' high rates of both infection and death. For this reason, the development of a vaccine that immunizes the receivers against both smallpox and anthrax would be great progress. This study seeks to develop such a vaccine by constructing a recombination plasmid that will introduce new genes that combat anthrax into the strain of vaccinia virus (VV), the virus used to vaccinate against smallpox. This study includes a highly detailed analysis of the various processes used to attempt this recombination and proposes plans further research into the subject.
ContributorsCameron, Jason (Author) / Stout, Valerie (Thesis director) / Jacobs, Bert (Committee member) / Hogan, Genevieve (Committee member) / Barrett, The Honors College (Contributor)
Created2003-05