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- Creators: School of Life Sciences
Description
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
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
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
Description
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
Description
Despite a continuously growing body of evidence that they are one of the major causes of pregnancy loss, preterm birth, pregnancy complications, and developmental abnormalities leading to high rates of morbidity and mortality, viruses are often overlooked and underestimated as teratogens. The Zika virus epidemic beginning in Brazil in 2015 brought teratogenic viruses into the spotlight for the public health community and popular media, and its infamy may bring about positive motivation and funding for novel treatments and vaccination strategies against it and a variety of other viruses that can lead to severe congenital disease. Lymphocytic choriomeningitis virus (LCMV) is famous in the biomedical community for its historic and continued utility in mouse models of the human immune system, but it is rarely a source of clinical concern in terms of its teratogenic risk to humans, despite its ability to cause consistently severe ocular and neurological abnormalities in cases of congenital infection. Possibilities for a safe and effective LCMV vaccine remain difficult, as the robust immune response typical to LCMV can be either efficiently protective or lethally pathological based on relatively small changes in the host type, viral strain, viral dose, method of infection/immunization, or molecular characteristics of synthetic vaccination. Introducing the immunologically unique state of pregnancy and fetal development to the mix adds complexity to the process. This thesis consists of a literature review of teratogenic viruses as a whole, of LCMV and its complications during pregnancy, of LCMV immunopathology, and of current understanding of vaccination against LCMV and against other teratogenic viruses, as well as a hypothetical experimental design intended to initially bridge the gaps between LCMV vaccinology and LCMV teratogenicity by bringing a vaccine study of LCMV into the context of viral challenge during pregnancy.
ContributorsHarris, Maryl (Author) / Blattman, Joseph (Thesis director) / Scotch, Matthew (Committee member) / Luna, Evelyn (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
This thesis discusses the complex situation involved in a person’s choice or means to vaccinate
themselves as well as their children. Included is a brief history on vaccines, a section describing
their mechanism of action, as well as information on how the vaccines work within our bodies.
The focus will then turn to the patient’s choice on whether or not to vaccinate themselves or their
child, including factors such as socioeconomic status, education level and their location. Within
this paper are the views of anti-vaccinators, as well as the views of pro-vaccinators and
suggestions on how to reeducate the public. I conclude that the AFIX model is of particular value
in public education: This involves Assessment of immunization coverage, Feedback in
informing providers of their performance, Incentives to help keep them motivated, and eXchange
of information which can be combined with incentives. While the AFIX model has focused on
doctors and nurses in the past, I conclude this model would be most effectively employed with
pharmacists, who see patients more routinely and often have higher levels of trust among the
general public.
themselves as well as their children. Included is a brief history on vaccines, a section describing
their mechanism of action, as well as information on how the vaccines work within our bodies.
The focus will then turn to the patient’s choice on whether or not to vaccinate themselves or their
child, including factors such as socioeconomic status, education level and their location. Within
this paper are the views of anti-vaccinators, as well as the views of pro-vaccinators and
suggestions on how to reeducate the public. I conclude that the AFIX model is of particular value
in public education: This involves Assessment of immunization coverage, Feedback in
informing providers of their performance, Incentives to help keep them motivated, and eXchange
of information which can be combined with incentives. While the AFIX model has focused on
doctors and nurses in the past, I conclude this model would be most effectively employed with
pharmacists, who see patients more routinely and often have higher levels of trust among the
general public.
ContributorsBernal-Fung, Yasmin (Author) / Martin, Thomas (Thesis director) / Morgan, Lawrence (Committee member) / School of Life Sciences (Contributor) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The objective of this thesis was to determine whether Zika Virus (ZIKV) can be effectively inactivated by Selective Photonic Disinfection (SEPHODIS) and determine whether key proteins involved in the infection process are preserved, making SEPHODIS a possible source for vaccine development. As of January 2018, there have been 3,720 confirmed cases of Congenital Zika Syndrome in infants, making a Zika Vaccine a high priority (Mitchell, 2018). SEPHODIS is a process that involves prolonged exposure of an object to a pulsing laser which can render it ineffective. Initially, ZIKV was subjected to laser inactivation for 6 hours, then a plaque assay was performed on both laser-treated and control samples. ZIKV was inactivated two-fold? after laser treatment, when compared with control, as indicated by the plaque assay results. Additionally, both samples were submitted to ELISA to evaluate antigenicity with a panel of monoclonal and human sera. As a second control, virus inactivated by formaldehyde (2%) was used. ELISA results showed that antigenicity of some proteins were preserved while others were probably disturbed. However, ELISA results show that ZIKV envelope protein (E-protein), the protein responsible for viral entry into cells, was effectively preserved after laser-treatment, implying that if laser parameters were tweaked to obtain more complete inactivation, then SEPHODIS may be an appropriate source for the development of a vaccine.
ContributorsViafora, Ataiyo Blue (Author) / Johnston, Stephen (Thesis director) / Tsen, Kong-Thon (Committee member) / School of Life Sciences (Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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