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- All Subjects: Creative Project
- All Subjects: Anxiety
- Creators: Department of Psychology
- Status: Published
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
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
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
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
Cancer is one of the leading causes of death in the world and represents a tremendous burden on patients, families and societies. S. Typhimurium strains are specifically attracted to compounds produced by cancer cells and could overcome the traditional therapeutic barrier. However, a major problem with using live attenuated Salmonella as anti-cancer agents is their toxicity at the dose required for therapeutic efficacy, but reducing the dose results in diminished efficacy. In this project, we explored novel means to reduce the toxicity of the recombinant attenuated Salmonella by genetically engineering those virulence factors to facilitate maximal colonization of tumor tissues and reduced fitness in normal tissues. We have constructed two sets of Salmonella strains. In the first set, each targeted gene was knocked out by deletion of the gene. In the second set, the predicted promoter region of each gene was replaced with a rhamnose-regulated promoter, which will cease the synthesis of these genes in vivo, a rhamnose-free environment.
ContributorsBenson, Lee Samuel (Author) / Kong, Wei (Thesis director) / Martin, Thomas (Committee member) / Lake, Douglas (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Center for Infectious Diseases and Vaccinology (Contributor) / School of Life Sciences (Contributor)
Created2013-05
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
This study was conducted to look at the possible effects of art intervention on anxiety levels of homeless young adults in a local drop-in shelter. While there is a fair amount of literature on art intervention and its applicability with vulnerable populations, its specific effect on anxiety has not been extensively examined. Researchers conducted two art interventions where state-trait anxiety (STAI Inventory) was measured before and after the interventions. Researchers hypothesized that anxiety would decrease after the art sessions. Some significant results were found. Participants reported feeling less strained (p = .041), worrying less over possible misfortunes (p = .02), feeling less nervous (p = .007) and feeling more decisive (p = .001). Future research recommendations are discussed.
ContributorsWille, Emma Margaret (Author) / Roe-Sepowitz, Dominique (Thesis director) / Mendoza, Natasha (Committee member) / Agliano, Stefania (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Social Work (Contributor) / Department of Psychology (Contributor)
Created2014-05