Matching Items (5)
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- All Subjects: Vaccines
- Creators: Hurlbut, Ben
- Status: Published
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
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
Vaccinations are important for preventing influenza infection. Maximizing vaccination uptake rates (80-90%) is crucial in generating herd immunity and preventing infection incidence. Vaccination of healthcare professionals (HCP) against influenza is vital to infection control in healthcare settings, given their consistent exposure to high-risk patients like: those with compromised immune systems, children, and the elderly (Johnson & Talbot, 2011). Though vaccination is vital in disease prevention, influenza vaccination uptake among HCP is low overall (50% on average) (Pearson et al., 2006). Mandatory vaccination policies result in HCP influenza vaccination uptake rates substantially higher than opt-in influenza vaccination campaigns (90% vs. 60%). Therefore, influenza vaccination should be mandatory for HCP in order to best prevent influenza infection in healthcare settings. Many HCP cite individual objections to influenza vaccination rooted in personal doubts and ethical concerns, not best available scientific evidence. Nevertheless, HCP ethical responsibility to their patients and work environments to prevent and lower influenza infection incidence overrules such individual objections. Additionally, mandatory HCP influenza vaccination policies respect HCP autonomy via including medical and religious exemption clauses. While vaccination as a prevention method for influenza is logically sound, individuals’ actions are not always rooted in logic. Therefore, I analyze HCP perceptions and actions toward influenza vaccination in an effort to better explain low HCP uptake rates of the influenza vaccine and individual objections to influenza vaccination. Such analysis can aid in gaining HCP trust when implementing mandatory HCP influenza vaccination policies. In summary, mandatory HCP influenza vaccination policies are ethically justified, effective, scientifically-supported method of maximizing HCP influenza vaccine uptake and minimizing the spread of the influenza virus within healthcare settlings.
ContributorsGur-Arie, Rachel (Author) / Maienschein, Jane (Thesis advisor) / Hurlbut, Ben (Thesis advisor) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2016
Description
Despite the approval of a Dengue virus (DV) vaccine in five endemic countries, dengue prevention would benefit from an immunization strategy highly immunogenic in young infants and not curtailed by viral interference. Problematically, infants younger than 9 year of age, whom are particularly prone to Dengue severe infection and death, cannot be immunized using current approved DV vaccine. The most important issues documented so far are the lack of efficiency and enhancement of the disease in young seronegative recipients, as well as uneven protection against the four DV serotypes. Based on data from clinical trials that showed enhanced performance of dengue vaccines when the host has previous anti-flaviviral immunity, I proposed here an attractive solution to complement the current vaccine: a recombinant measles vaccine vectoring dengue protective antigens to be administered to young infants. I hypothesized that recombinant measles virus expressing Dengue 2 and 4 antigens would successfully induce neutralizing responses against DV2 and 4 and the vaccine cocktail of this recombinant measles can prime anti-flaviviral neutralizing immunity. For this dissertation, I generated and performed preclinical immune assessment for four novel Measles-Dengue (MV-DV) vaccine candidates. I generated four MVs expressing the pre membrane (prM) and full length or truncated (90%) forms of the major envelope (E) from DV2 and DV4. Two virus, MVvac2-DV2(prME)N and MVvac2-DV4(prME), expressed high levels of membrane associated full-length E, while the other two viruses, MVvac2-DV2(prMEsol)N and MVvac2-DV4(prMEsol)N, expressed and secreted truncated, soluble E protein to its extracellular environment. The last two vectored vaccines proved superior anti-dengue neutralizing responses comparing to its corresponding full length vectors. Remarkably, when MVvac2-DV2/4(prMEsol)N recombinant vaccines were combined, the vaccine cocktail was able to prime cross-neutralizing responses against DV 1 and the relatively distant 17D yellow fever virus attenuated strain. Thus, I identify a promising DV vaccination strategy, MVvac2-DV2/4(prMEsol)N, which can prime broad neutralizing immune responses by using only two of the four available DV serotypes. The current MV immunization scheme can be advantageus to prime broad anti-flaviviral neutralizing immunity status, which will be majorly boosted by subsequent chimeric Dengue vaccine approaches.
ContributorsAbdelgalel, Rowida (Author) / Reyes del Valle, Jorge (Thesis advisor) / Mason, Hugh (Thesis advisor) / Lake, Douglas (Committee member) / Stout, Valerie (Committee member) / Frasch, Wayne (Committee member) / Arizona State University (Publisher)
Created2016
Description
In 1996, President Clinton ordered the formation of the Advisory Committee on Human Radiation Experiments (ACHRE), which undertook to evaluate the morality of a myriad of secret and publicized radiation experiments ranging from 1944 to 1974. The goal of this thesis is to analyze the ways in which that committee formed moral evaluations and the extent to which its strategies related to a broader historical and philosophical discourse. Here I attempt to describe two specific techniques of simplification the committee deploys in order to make a retrospective moral analysis possible. Although the techniques comprise specific problems, frameworks, subjective perspectives, and conceptual links, their unifying principle is the field of choices the techniques produce. In the first technique I outline, I argue that by focusing on the problem of historical relativism, the committee gains a platform through which it would be granted flexibility in making a distinction between moral wrongdoing and blameworthiness. In the second technique of simplification I outline, I argue that the committee's incorporation of a principle to reduce uncertainty as an ethical aim allow it to establish new ways to reconcile scientific aims with moral responsibility. In addition to describing the structure of these techniques, I also demonstrate how they relate to the specific experiments the analysts aim to evaluate, using both the ACHRE experiments as well as the Nuremberg Trial experiments as my examples. My hope is not to show why a given committee made a particular moral evaluation, or to say whether a decision was right or wrong, but rather to illustrate how certain techniques open up a field of choices that allow moral analysts to form retrospective moral judgments.
ContributorsCirjan, Cristian (Author) / Hurlbut, Ben (Thesis director) / Humphrey, Ted (Committee member) / Zachary, Gregg (Committee member) / Barrett, The Honors College (Contributor)
Created2015-05