Matching Items (19)

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The Development of a Plant-Expressed M2e-Based Universal Influenza Vaccine

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,

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.

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Date Created
  • 2018-05

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An Assessment of Vaccine Hesitancy in the context of the Flu in Maricopa County, Arizona

Description

Objective: To provide insight into the World Health Organization SAGE Working Group Vaccine Hesitancy Survey by applying the tool to populations across Maricopa County, Arizona. Design: An online survey was

Objective: To provide insight into the World Health Organization SAGE Working Group Vaccine Hesitancy Survey by applying the tool to populations across Maricopa County, Arizona. Design: An online survey was conducted using the Qualtrics Survey Software, of individuals residing in Maricopa County, Arizona during the month of October 2019. Results: Of 209 respondents, the followed demonstrated to be the top 3 reasons for either having not received the flu shot yet or having not planned to receive the flu shot: “I’m healthy, I don’t need it”(20.1%); “Worried I might get the flu from it”(17.7%); “I don’t think it works”(17.7%) Statistical analysis demonstrated that vaccine hesitant and non-hesitant respondents are likely to respond differently to topics covering: safety of vaccines; self-perceived health status; importance of the flu shot among one’s peers; flu vaccine related knowledge Conclusions: The WHO VHS applied to the population of Maricopa County, Arizona reported little hesitancy towards the seasonal flu vaccine. Statistical analysis of Vaccine Hesitant respondents vs. Non-Hesitant respondents demonstrates that specified public health education focused on the immunological implications of vaccines may be needed for the hesitant population to gain confidence in vaccine efficacy. A more diverse respondent group that consists of residents beyond the county lines of Maricopa is needed to understand the full scope of vaccine hesitancy that exists in Arizona.

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Date Created
  • 2020-05

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Phylogeography of Influenza in the Southwest United States

Description

Influenza remains a constant concern for public health agencies across the nation and worldwide. Current methods of surveillance suffice but they fall short of their true potential. Incorporation of evolutionary

Influenza remains a constant concern for public health agencies across the nation and worldwide. Current methods of surveillance suffice but they fall short of their true potential. Incorporation of evolutionary data and analysis through studies such as phylogeography could reveal geographic sources of variation. Identification and targeting of such sources for public health initiatives could yield increased effectiveness of influenza treatments. As it stands there is a lack of evolutionary data available for such use, particularly in the southwest. Our study focused on the sequencing and phylogeography of southwestern Influenza A samples from the Mayo Clinic. We fully sequenced two neuraminidase genes and combined them with archived sequence data from the Influenza Research Database. Using RAxML we identified the clade containing our sequences and performed a phylogeographic analysis using ZooPhy. The resultant data were analyzed using programs such as SPREAD and Tracer. Our results show that the southwest sequences emerged from California and the ancestral root of the clade came from New York. Our Bayesian maximum clade credibility (MCC) tree data and SPREAD analysis implicates California as a source of influenza variation in the United States. This study demonstrates that phylogeography is a viable tool to incorporate evolutionary data into existing forms of influenza surveillance.

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Created

Date Created
  • 2013-05

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Determination of 5-5 Synbody Protein Target and Mechanism of Binding to Influenza Virus

Description

The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus

The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus and there are a number of therapeutics which have proven effective in aiding people infected with the virus. However, these therapeutics are subject to various limitations including increased resistance, limited supply, and significant side effects. A new therapeutic is needed which addresses these problems and protects people from the influenza virus. Synbodies, synthetic antibodies, may provide a means to achieve this goal. Our group has produced a synbody, the 5-5 synbody, which has been shown to bind to and inhibit the influenza virus. The direct pull down and western blot techniques were utilized to investigate how the synbody bound to the influenza virus. Our research showed that the 5-5 synbody bound to the influenza nucleoprotein (NP) with a KD of 102.9 ± 74.48 nM. It also showed that the synbody bound strongly to influenza viral extract from two different strains of the virus, the Puerto Rico (H1N1) and Sydney (H3N2) strains. This research demonstrated that the 5-5 synbody binds with high affinity to NP, which is important because influenza NP is highly conserved between various strains of the virus and plays an important role in the replication of the viral genome. It also demonstrated that this binding is conserved between various strains of the virus, indicating that the 5-5 synbody potentially could bind many different influenza strains. This synbody may have potential as a therapeutic in the future if it is able to demonstrate similar binding in vivo.

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Created

Date Created
  • 2014-05

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University Student Knowledge and Perception of Influenza

Description

Influenza has shown its potential to affect and even kill millions of people within an extremely short time frame, yet studies and surveys show that the general public is not

Influenza has shown its potential to affect and even kill millions of people within an extremely short time frame, yet studies and surveys show that the general public is not well educated about the facts about influenza, including prevention and treatment. For this reason, public perception of influenza is extremely skewed, with people generally not taking the disease as seriously as they should given its severity. To investigate the inconsistencies between action and awareness of best available knowledge regarding influenza, this study conducted literature review and a survey of university students about their knowledge, perceptions, and action taken in relationship to influenza. Due to their dense living quarters, constant daily interactions, and mindset that they are "immune" to fairly common diseases like influenza, university students are a representative sample of urban populations. According to the World Health Organization (WHO), 54% of the world's population lived in cities as of 2014 (Urban population growth). Between 2015 and 2020, the global urban population is expected to grow 1.84% per year, 1.63% between 2020 and 2025, and 1.44% between 2025 and 2030 (Urban population growth). Similar projections estimate that by 2017, an overwhelming majority of the world's population, even in less developed countries, will be living in cities (Urban population growth). Results of this study suggest possible reasons for the large gap between best available knowledge and the perceptions and actions of individuals on the other hand. This may lead to better-oriented influenza education initiatives, more effective prevention and treatment plans, and generally raise excitement and awareness surrounding public health and scientific communication.

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Created

Date Created
  • 2014-12

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Analysis of Inhibition of Influenza Replication via Synthetic Antibodies

Description

The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center

The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.

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Created

Date Created
  • 2014-05

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Quantifying the Mortality Impact of the 1918-1919 Influenza Pandemic in Arizona

Description

Mortality of 1918 influenza virus was high, partly due to bacteria coinfections. We characterize pandemic mortality in Arizona, which had high prevalence of tuberculosis. We applied regressions to over 35,000

Mortality of 1918 influenza virus was high, partly due to bacteria coinfections. We characterize pandemic mortality in Arizona, which had high prevalence of tuberculosis. We applied regressions to over 35,000 data points to estimate the basic reproduction number and excess mortality. Age-specific mortality curves show elevated mortality for all age groups, especially the young, and senior sparing effects. The low value for reproduction number indicates that transmissibility was moderately low.

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Created

Date Created
  • 2015-05

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Mortality and Transmissibility Patterns of the 1957 Influenza Pandemic in Maricopa County, Arizona

Description

Background: While research has quantified the mortality burden of the 1957 H2N2 influenza pandemic in the United States, little is known about how the virus spread locally in Arizona, an

Background: While research has quantified the mortality burden of the 1957 H2N2 influenza pandemic in the United States, little is known about how the virus spread locally in Arizona, an area where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.
Methods: Using archival death certificates from 1954 to 1961, this study quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and generation intervals of 3 and 4 days. Local newspaper articles from The Arizona Republic were analyzed from 1957-1958.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 17.85 in the elderly (≥65 years). All other age groups had extremely low excess-mortality and the typical U-shaped age-pattern was absent. However, relative risk was greatest (3.61) among children and young adolescents (5-14 years) from October 1957-March 1958, based on incidence rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was 1.08-1.11, assuming 3 or 4 day generation intervals and exponential or fixed distributions.
Conclusions: Maricopa County largely avoided pandemic influenza from 1957-1961. Understanding this historical pandemic and the absence of high excess-mortality rates and transmissibility in Maricopa County may help public health officials prepare for and mitigate future outbreaks of influenza.

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Date Created
  • 2015-05

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Increasing Influenza Immunization Rates at a Homeless Clinic Through Staff Education

Description

Background: Healthy People 2020, a government organization that sets health goals for the United States, has established the benchmark objective of 70% influenza vaccination coverage. National trends show immunization rates

Background: Healthy People 2020, a government organization that sets health goals for the United States, has established the benchmark objective of 70% influenza vaccination coverage. National trends show immunization rates are a dismal 41.7% for the adult population. Persons
experiencing homelessness are a vulnerable population in which access to preventative health care services is lacking. Prevention of acute illness, whenever possible, is crucial to maintaining the health of this population. The purpose of this project is to increase influenza vaccinations through staff education at a homeless clinic.

Methods: Eighty-eight volunteer staff, at a student led homeless clinic, received education on the influenza vaccinations. The education occurred at the first orientation meeting of the fall semester in 2016 and consisted of; the importance of immunizations, goals of Healthy People 2020, and an emphasis on addressing patient objections. The effectiveness of the program
compared the percentage of patients immunized from August - December 2016 to 2015.

Results: Post intervention, 44% of the clinic patients were immunized against influenza,
compared to 18% (pre-intervention). This finding resulted in a statistically significant increase in
vaccinations (Z= -5.513, p= < .001, Wilcoxon signed rank test). Eighty-eight volunteers were
present at the influenza vaccination educational intervention and 82 returned their surveys
(response rate 93%). The average score of the posttest was 96% (range 70-100%).

Conclusions: These findings support staff education on influenza vaccinations as a strategy for
increasing vaccination in the homeless population. Such interventions provide promise to
increase influenza vaccinations, however, they fall short of meeting the goals of Healthy People
2020. Identifying innovative interventions is critical to meet the goals of Healthy People 2020.

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Agent

Created

Date Created
  • 2017-04-17

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Utilizing Technology to Affect Influenza Vaccine Coverage Among Children with Chronic Respiratory Conditions

Description

Purpose: To integrate text messaging into a multi-component reminder system to improve influenza vaccination rates among children with chronic respiratory conditions.

Background: Influenza presents burdens for children with chronic respiratory

Purpose: To integrate text messaging into a multi-component reminder system to improve influenza vaccination rates among children with chronic respiratory conditions.

Background: Influenza presents burdens for children with chronic respiratory conditions including increased mortality, morbidity, hospitalizations, and decreased quality of life for children and caregivers. Influenza vaccinations may reduce these complications yet approximately half of children remain unprotected annually. Synthesized evidence supports integration of text messaging into a multi-component strategy to increase the influenza vaccination rate in many populations of interest.

Methods: The intervention was a single text message and electronic mail message sent to all families in a private pediatric pulmonology practice who enabled text and/or electronic mail messages in the patient portal. A follow-up survey assessed various aspects of message receipt. Surveys were completed without collection of demographic information.

Results: Electronic mail messages were sent to 3140 addresses available in the patient portal. The number of text messages sent out via the patient portal was 75 with 66 (88%) delivered successfully. Follow-up surveys were initiated by 107 recipients. Frequency analysis showed that participants preferred text and electronic mail messages over other forms of communication. A statistically significant positive relationship was found utilizing Chi Square between those who received a message and those whose child received an influenza vaccination (p= .027).

Conclusions: Text and electronic mail messaging are cost-effective and well-received forms of communication that can be easily integrated into existing systems. These delivery routes are translatable to many populations and can convey various types of messages.

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Created

Date Created
  • 2016-05-03