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Biological and immunological characterization of plant-produced HIV-1 Gag/dgp41 virus-like particles
Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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
My project is designed to provide art education to incarcerated youth in Arizona. This project will address two current issues in Arizona; the underfunding of art programs and high rates of incarceration. As of 2021, there are no state-funded art programs in Arizona. Arizona is tied with Texas for the eighth highest rate of incarceration in the country. In Arizona, 750 out of every 100,000 people are incarcerated. This project is an art course for incarcerated youth. The project includes a packet detailing the course content and assignment details, a class syllabus, a course flyer, and a certificate of completion. The course is intended to be taught at the Adobe Mountain School facility. The course is designed so that it can be implemented in other facilities in the future. The class will be taught by volunteers with a background in studio art, design, or art education. Each student will receive a course packet that they can use to keep track of information and assignments. Instructors will use the course packet to teach the class. The course focuses on drawing with charcoal and oil pastel, which will build a foundation in drawing skills. The course covers a twelve-week semester. The course content packet includes a week-by-week breakdown of the teaching material and project descriptions. The course consists of two main projects and preparatory work. The preparatory work includes vocabulary terms, art concepts, drawing guides, brainstorming activities, and drawing activities. The two main prompts are designed for students to explore the materials and to encourage self-reflection. The class is curated so that students can create art in a low-risk, non-judgemental environment. The course will also focus on establishing problem-solving and critical thinking skills through engaging activities.
ContributorsSheppard, Eve (Author) / Cornelia, Wells (Thesis director) / Jennifer, Nelson (Committee member) / School of Art (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
ABSTRACT In terms of prevalence, human suffering and costs dengue infections are the most important arthropod-borne viral disease worldwide. Dengue virus (DENV) is a mosquito-borne flavivirus and the etiological agent of dengue fever and dengue hemorrhagic fever. Thus, development of a safe and efficient vaccine constitutes an urgent necessity. Besides the traditional strategies aim at generating immunization options, the usage of viral vectors to deliver antigenic stimulus in order to elicit protection are particularly attractive for the endeavor of a dengue vaccine. The viral vector (MVvac2) is genetically equivalent to the currently used measles vaccine strain Moraten, which adds practicality to my approach. The goal of the present study was to generate a recombinant measles virus expressing structural antigens from two strains of DENV (DENV2 and DENV4) The recombinant vectors replication profile was comparable to that of the parental strain and expresses either membrane bound or soluble forms of DENV2 and DENV4 E glycoproteins. I discuss future experiments in order to demonstrate its immunogenicity in our measles-susceptible mouse model.
ContributorsAbdelgalel, Rowida (Author) / Reyes del Valle, Jorge (Thesis advisor) / Hogue, Brenda (Committee member) / Frasch, Wayne D (Committee member) / Arizona State University (Publisher)
Created2013
Description
"On Music Videos" is an exploration of music videos, particularly narrative ones. As such, a brief history of the music video and its genres are examined. Ideas about narrative are also discussed through descriptions of what is meant by "story," based on theories from Pixar animators as well as author J.R.R. Tolkien. The connections between how story fits with music videos is then outlined. From this background research one is able to analyze examples of existing narrative music videos, before applying this knowledge and reflecting on the process of creating a narrative music video.
ContributorsNguyen, Melissa M (Author) / Finn, Ed (Thesis director) / Simeone, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Art (Contributor) / School of Arts, Media and Engineering (Contributor)
Created2015-05
Description
Many studies have supported the theory that gain-framed messaging is effective in changing smoking behavior. However, the importance of focusing on long-term positive benefits or short-term positive benefits in this messaging remains a mystery. This study investigated the role that reward-delay within gain-framed messaging has on the self-esteem and behavior of cigarette smokers. Specifically, it sought to answer the question of whether short-term reward-delay messaging is more effective in increasing self-esteem and positive smoking behavior than long-term reward-delay messaging. An intervention was conducted in which participants, 16 female and 17 male, were exposed to either short-term reward-delay information or long-term reward-delay information. Self-esteem scores as well as smoking behavior were measured and compared before and after the intervention. Results from the study showed that participants in the short-term reward-delay group smoked 2 less cigarettes per day and 12 less cigarettes per week on average after the intervention than participants in the long-term reward-delay group. The results were also consistent with the findings of previous studies that suggest females are more heavily influenced by gain-framed messaging than males.
ContributorsHintze, Kellie Elizabeth (Author) / Chisum, Jack W. (Thesis director) / Brown, Carla J. (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Dysmorphia is a series of large-scale paintings that address the relationship between a body image disorder called Body Dysmorphia (BDD) and plastic surgery. The audience sees women of all colors, shapes and sizes in their most vulnerable state. However, the shapes of their bodies and the abnormal background are not what we are used to seeing. Presented in the IAP Studios, Dysmorphia aims to start a conversation around the rising global occurrences of cosmetic procedures, the patients who suffer from Body Dysmorphia, and how the two subjects relate. Plastic surgery is a highly controversial conversation that the world is currently having. However, BDD is not a common topic that comes up within those discussions. Many surgeons may not realize or choose to ignore the fact that a vast majority of their patients have a body image disorder. Sometimes the patients themselves may not even realize it. Whether we believe plastic surgery is a positive life-changing choice or that it takes advantage of those who have disorders such as BDD, the end result will be up to the audience to determine. By establishing a connection between the two contrasting ideals, society can then begin to identify where they might fit in the conversation. Dysmorphia aims to spark informative discussions about these kinds of social issues by exploring the female body and bringing to light plastic surgery's attempt to alter it.
ContributorsArnold, Brittany Marie (Author) / Kim, Marianne (Thesis director) / Clark, Patricia (Committee member) / School of Art (Contributor) / School of Humanities, Arts, and Cultural Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Abstract Retrograde presents questions about the creation and value of art through a graphic novel. Materials used to create the work were illustration paper, ink, brushes, and printed screen tones. The piece was created in four stages: first, each panel was sketched into the first draft; second, the sketch was researched and fully developed into a complete drawing; third, the sketch was completely traced with ink and texture was added; finally, the drawing tones were added with ink and screen tones. The plot of Retrograde revolves around the protagonist, Vera, as she attempts to find a place for her art in an artistic community that rejects her for her lack of commercial success and for the advantages she got through connections. When Vera appears to have succeeded, a sudden plot twist reveals a conspiracy which undermines her success. By following Vera, the novel illustrates a corrupt artistic society in which the value of art is established by a small amount of artistic elites. The written portion of the project expounds on the various ideas that drove the novel, including how art forms like graphic novels come to be situated low in artistic hierarchies and how interpretations can be negatively guided by already established institutions. Among some of the theorists referenced within the paper are Walter Benjamin, Clement Greenberg, and Susan Sontag. In conclusion, the project illustrates an inclination to judge art by potential commercial value and by already established hierarchies, limiting the possibilities of new interpretations and shifts in those same hierarchies. Keywords: art, art theory, graphic novels
ContributorsCervantes, Liliana (Author) / Dove-Viebahn, Aviva (Thesis director) / Solis, Forrest (Committee member) / School of Humanities, Arts, and Cultural Studies (Contributor) / School of Art (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
‘why we bend' a Bachelor of Fine Arts honors thesis exhibition by Ximenna Hofsetz and Tiernan Warner brings together installation, digital, sculptural, and printed artwork. The main focus concerns memory; and its vague, formless, and hazy nature. The work also examines what would happen if cognitive space could be physically mapped? What would it look like in sculptural form? Memory erodes and distorts with time. We influence our memories as much as they affect us. Thus, just as relationships are ever-changing, and our memories of those we interact with constantly shifting, our relationships with our own memories are malleable and evolve through time. This transient nature of memory is depicted in the various stylistic means of this exhibition by referencing time and space as well as personal memories and ephemera in both concrete and abstract ways. ‘why we bend’ implements a variety of multimedia techniques to examine recollection and its hold on us.
ContributorsHofsetz, Ximenna Cedella (Author) / Gutierrez, Rogelio (Thesis director) / Hood, Mary (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Art (Contributor)
Created2014-12
Description
Poetry serves as a window through which we can convey emotions and experiences otherwise difficult to access and express. This chapbook addresses the moments in life that have dramatic transformational effects and those moments and events we wish to deny. Through my poetry, I reveal the honest revelations of hurt and pain, and the raw emotions evoked from the things that have occurred throughout my life. In doing so, I confront these painful experiences from a place of conscious awareness of the way in which they have impacted my life, and I allow others access to my hurt, self-hatred, and imperfection acknowledged throughout. This chapbook symbolizes the movement from a place of denial to a place of awareness and finally to a place of transformation and growth. As my poetry transformed from weak poems only accessible on an abstract level to powerful poems of honest and tangible pain and hurt, I experienced my own transformation. Allowing myself to candidly share my experiences with others has enabled me to grow from these experiences.
ContributorsLarson, Amanda Beth (Author) / Montesano, Mark (Thesis director) / Comeaux, Alexandra (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / Department of Psychology (Contributor)
Created2014-12