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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

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

The Founders lab is a year-long program that gives its students an opportunity to participate in a unique team-based, experiential Barrett honors thesis project to design and apply marketing and sales strategies, as well as business and financial models to start up and launch a new business. This honors thesis

The Founders lab is a year-long program that gives its students an opportunity to participate in a unique team-based, experiential Barrett honors thesis project to design and apply marketing and sales strategies, as well as business and financial models to start up and launch a new business. This honors thesis project focuses on increasing the rate of vaccination outcomes in a country where people are increasingly busy (less time) and unwilling to get a needle through a new business venture that provides a service that brings vaccinations straight to businesses, making them available for their employees. Through our work with the Founders Lab, our team was able to create this pitch deck.

ContributorsZatonskiy, Albert (Co-author) / Hanzlick, Emily (Co-author) / Gomez, Isaias (Co-author) / Byrne, Jared (Thesis director) / Hall, Rick (Committee member) / Silverstein, Taylor (Committee member) / Department of Finance (Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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

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
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In the United States, a dispute has arisen over the safety and need for vaccination, particularly in regard to compulsory vaccination laws. New outlets and social media sites publish countless reports about the dangers of vaccines or of known adverse reactions as well as imagined or unproven worries. Individuals' rights

In the United States, a dispute has arisen over the safety and need for vaccination, particularly in regard to compulsory vaccination laws. New outlets and social media sites publish countless reports about the dangers of vaccines or of known adverse reactions as well as imagined or unproven worries. Individuals' rights to choose to get vaccinated or allow their children to be vaccinated comes to direct conflict with measures needed to protect communities from preventable viral diseases. The controversy surrounding vaccines is not new, nor necessarily are the fundamental reasons for skepticism. Looking back through the history of vaccines as a medical tool, the evolution of the controversy can be observed taking place with each new historical context, scientific development, and social conditions. Despite scientific research and assurances of vaccine safety, opposition and unease about vaccination appear to take Looking individually at the development and distribution of the smallpox (variola virus), polio (poliovirus) and human papilloma virus(HPV) vaccines, concerns regarding the violation of personal rights, safety of vaccines themselves, and social stigmas and connotations surrounding vaccines can be seen to evolve and change. Due to the way doubt can manifest in different ways over time, it may be impossible to fully end the vaccine debate. However, nderstanding the sociological factors behind anti-vaccine sentiment may allow healthcare professionals to work with concerned people with a particular care to address these visceral and sometimes irrational fears surrounding vaccination.
ContributorsStevens, Luke Christian (Author) / Jacobs, Bertram (Thesis director) / Washo-Krupps, Delon (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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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 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
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The objectives of this review include a discussion of the West Nile Virus phylogeny, transmission history, how the virus functions in the body and how it is a threat to public health, and then discusses these items related to vaccine technology surrounding West Nile Virus. This will include past developments,

The objectives of this review include a discussion of the West Nile Virus phylogeny, transmission history, how the virus functions in the body and how it is a threat to public health, and then discusses these items related to vaccine technology surrounding West Nile Virus. This will include past developments, current research in the field and what it may take to develop such a vaccine safe and economical for human usage.
ContributorsSlinker, Haleigh Renee (Author) / Chen, Qiang (Thesis director) / Huffman, Holly (Committee member) / Oberstein, Bruce (Committee member) / Barrett, The Honors College (Contributor) / School of Letters and Sciences (Contributor)
Created2013-05
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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

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
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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

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
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Moraxella catarrhalis is a gram negative commensal bacteria that is a primary cause of otitis media in infants and severe exacerbations of COPD in adults. M. catarrhalis treatment has become increasingly difficult and expensive over the past half-century due to the emergence of beta-lactamase producing strains. There are currently no

Moraxella catarrhalis is a gram negative commensal bacteria that is a primary cause of otitis media in infants and severe exacerbations of COPD in adults. M. catarrhalis treatment has become increasingly difficult and expensive over the past half-century due to the emergence of beta-lactamase producing strains. There are currently no vaccines available to protect against infections. In this paper, we propose a transcriptomics-based approach for identifying potential vaccine targets. Additionally, a novel method was used to create bacterial vaccine polypeptides composed of sequence conserved peptides secreted through the outer membrane. Polypeptides were tested for immunogenicity and protective capacity in mice. We show that relative abundance of outer membrane proteins does not correlate with immunogenicity. We also show promising results for polypeptide protection in a mouse pulmonary clearance model.

ContributorsRobinson, Aspen Grace (Author) / Stull, Terrence (Thesis director) / Whitby, Paul (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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In this study, we investigated the inactivation of wild-type vMyx-GFP (MYXV) using different methods. Assays were performed in vitro to test the following inactivation methods: heat, longwave UV only, longwave UV with psoralen (P + LWUV), and psoralen (P) only. In vitro assays demonstrated that the psoralen alone treatment did

In this study, we investigated the inactivation of wild-type vMyx-GFP (MYXV) using different methods. Assays were performed in vitro to test the following inactivation methods: heat, longwave UV only, longwave UV with psoralen (P + LWUV), and psoralen (P) only. In vitro assays demonstrated that the psoralen alone treatment did not cause any inactivation. These results showed that effective inactivation using psoralen was likely reliant on subsequent UV irradiation, creating a synergistic effect. Additionally, the UV and P + LWUV treatment demonstrated inactivation of MYXV, although by different mechanisms, as the UV-only treated virus demonstrated background infection, while P + LWUV treated virus did not. In mice, P + LWUV and UV treatment of MYXV demonstrated to be effective inactivation methods and likely preserved the antigenic epitopes of MYXV, allowing for the production of neutralizing antibodies in mice. More research is recommended on the heat treatment of MYXV as neutralizing antibodies were not observed, possibly due to the treatment denaturing antigenic epitopes or needing more booster injections to reach the threshold antibody concentration for protection. Furthermore, we demonstrated that the intraperitoneal (IP) injection of inactivated MYXV was superior to the subcutaneous injection in eliciting a strong immune response. The increased neutralizing antibodies observed after IP injection could be due to the advantage that the IP route has of reaching lymphoid tissue faster.

ContributorsSprout, Jamie (Co-author) / Davoudi, Sahar (Co-author) / McFadden, Grant (Thesis director) / Rahman, Masmudur (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05