Matching Items (35)

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Use of a Recombinant Vaccinia Virus Expressing Interferon Gamma for Post-Exposure Protection against Vaccinia and Ectromelia Viruses

Description

Post-exposure vaccination with vaccinia virus (VACV) has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy

Post-exposure vaccination with vaccinia virus (VACV) has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy of post-exposure vaccination this has not been definitively studied in humans. In this study, we analyzed post-exposure prophylaxis using several attenuated recombinant VACV in a mouse model. A recombinant VACV expressing murine interferon gamma (IFN-γ) was most effective for post-exposure protection of mice infected with VACV and ectromelia virus (ECTV). Untreated animals infected with VACV exhibited severe weight loss and morbidity leading to 100% mortality by 8 to 10 days post-infection. Animals treated one day post-infection had milder symptoms, decreased weight loss and morbidity, and 100% survival. Treatment on days 2 or 3 post-infection resulted in 40% and 20% survival, respectively. Similar results were seen in ECTV-infected mice. Despite the differences in survival rates in the VACV model, the viral load was similar in both treated and untreated mice while treated mice displayed a high level of IFN-γ in the serum. These results suggest that protection provided by IFN-γ expressed by VACV may be mediated by its immunoregulatory activities rather than its antiviral effects. These results highlight the importance of IFN-γ as a modulator of the immune response for post-exposure prophylaxis and could be used potentially as another post-exposure prophylaxis tool to prevent morbidity following infection with smallpox and other orthopoxviruses.

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Date Created
  • 2013-10-17

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Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques

Description

Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein

Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4[superscript +] and CD8[superscript +] Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4[superscript +] T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1.

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Date Created
  • 2016-04-14

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Characterization of the Physiological Response following In Vivo Administration of Astragalus membranaceus

Description

The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates

The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates the physiological responses to A. membranaceus by measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after the in vivo administration of A. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8–12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-γ and tumor necrosis factor-α, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role of A. membranaceus in priming for a potential immune response as well as its effect on blood flow and wound healing.

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Date Created
  • 2016-03-30

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Inhibition of PKR phosphorylation by Vaccinia Virus' E3 Protein

Description

Vaccinia virus is a cytoplasmic, double-stranded DNA orthopoxvirus. Unlike mammalian cells, vaccinia virus produces double-stranded RNA (dsRNA) during its viral life cycle. The protein kinase R, PKR, is one of

Vaccinia virus is a cytoplasmic, double-stranded DNA orthopoxvirus. Unlike mammalian cells, vaccinia virus produces double-stranded RNA (dsRNA) during its viral life cycle. The protein kinase R, PKR, is one of the principal host defense mechanisms against orthopoxvirus infection. PKR can bind double-stranded RNA and phosphorylate eukaryotic translation initiation factor, eIF2α, shutting down protein synthesis and halting the viral life cycle. To combat host defenses, vaccinia virus encodes E3, a potent inhibitor of the cellular anti-viral eIF2α kinase, PKR. The E3 protein contains a C-terminal dsRNA-binding motif that sequesters dsRNA and inhibits PKR activation. We demonstrate that E3 also interacts with PKR by co-immunoprecipitation. This interaction is independent of the presence of dsRNA and dsRNA-binding by E3, indicating that the interaction is not due to dsRNA-bridging.
PKR interaction mapped to a region within the dsRNA-binding domain of E3 and overlapped with sequences in the C-terminus of this domain that are necessary for binding to dsRNA. Point mutants of E3 were generated and screened for PKR inhibition and direct interaction. Analysis of these mutants demonstrates that dsRNA-binding but not PKR interaction plays a critical role in the broad host range of VACV. Nonetheless, full inhibition of PKR in cells in culture requires both dsRNA-binding and PKR interaction. Because E3 is highly conserved among orthopoxviruses, understanding the mechanisms that E3 uses to inhibit PKR can give insight into host range pathogenesis of dsRNA producing viruses.

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Date Created
  • 2017-05

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Understanding Bioethical Concerns of Laboratory Research: A Case Study On Discovering Programmed Necrosis Pathways

Description

The concept of “good” research is concrete in terms of technique, but complex in theory. As technology advances, the complexity of problems we must solve also grows. Research is facing

The concept of “good” research is concrete in terms of technique, but complex in theory. As technology advances, the complexity of problems we must solve also grows. Research is facing an ethical dilemma—which projects, applied or basic, should be funded. Research is no longer an isolated sector in society, and the decisions made inside of the laboratory are affecting the general public more directly than ever before. While there is no correct answer to what the future of research should be, it is clear that good research can no longer be only defined by the current classification system, which is rooted in antiquated, yet ingrained, social status distinctions.
Differences between basic and applied research were explored through a wet-lab case study. Vaccinia virus (VACV) infections are a prime model of the competition between a virus and its host. VACV contains a gene that is highly evasive of the host immune system, gene E3L. The protein encoded by E3L is E3, which contains two highly conserved regions, a C-terminus, and a N-terminus. While the C-terminus is well-understood, the mechanism by which the N-terminus grants IFN resistance was previously unknown. This project demonstrated that the N-terminus prevents the initiation of programmed necrosis through host-encoded cellular proteins RIP3 and DAI. These findings provide insight into the function of the N-terminus of E3, as well as the unique functions of induced programmed necrosis.
This project was an example of “basic” research. However, it highlights the interconnectivity of basic and applied research and the danger in isolating both projects and perspectives. It points to the difficult decisions that must be made in science, and the need for a better research classification system that considers what makes science “good” outside of antiquated social class ideologies that have shaped science since ancient Greece. While there are no easy answers to determine what makes research “good,” thinking critically about the types of research projects that will be pursued, and the effects that research has on both science and society, will raise awareness, initiate new conversations, and encourage more dialogue about science in the 21st century.

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Date Created
  • 2016-12

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MTC Transmission of HIV in sub-Saharan Africa: Barriers and Solutions to Implementation of the WHO's Treatment Plans

Description

Human Immunodeficiency Virus, or HIV, is a global epidemic, costing over 9.51 million individuals their lives since 2000. There are different modes of transmission of HIV, one such mode being

Human Immunodeficiency Virus, or HIV, is a global epidemic, costing over 9.51 million individuals their lives since 2000. There are different modes of transmission of HIV, one such mode being from an HIV positive woman to her child before, during, or after delivery (SIC Curriculum, 2006). Though a global epidemic, not all countries have the same prevalence of mother to child, or MTC, transmission of HIV. In 2016, over 160,000 children under the age of five were newly infected with HIV in sub-Saharan Africa. That is compared to the United States of America, where it is estimated that fewer than 150 new infant HIV infections occur yearly (Glaser Foundation, 2020). Those differences exist despite both countries having access to preventative medication as of 1998.
Additionally, the World Health Organization, or WHO, developed three treatment plans for prevention of MTC transmission of HIV, globally available as of 2010 (WHO, 2010). The goal of the WHO was to globally standardize care of HIV-positive pregnant women and their infants in order to decrease the global prevalence of HIV. The first plan was called Option A, then came Option B, and lastly Option B+. While preventative medication has been available for over twenty years and at least one of these theoretically effective treatment plans has been implemented and is readily available in each country of sub-Saharan Africa, the overall prevalence of MTC transmission of HIV in sub-Saharan Africa has continued to be notably high compared to other countries. Thus, the aim of this thesis is to explore some of the significant obstacles to implementation of the WHO’s treatment plans in sub-Saharan Africa that contribute to that high prevalence. I also suggest possible solutions to those barriers in order to effectively decrease the prevalence of MTC transmission of HIV.

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Date Created
  • 2020-05

HIV Stigma: A Research and Art Investigation

Description

In the years following the HIV epidemic, much has changed in the way of public health, the social epidemic of stigma has remained. It is the assertion of the authors

In the years following the HIV epidemic, much has changed in the way of public health, the social epidemic of stigma has remained. It is the assertion of the authors that stigma can be combatted through the propagation of accurate education and exposure to the lasting negative impacts of social stigma on persons living with HIV in the United States at present. Although individuals who are not apart of this community cannot truly understand the impacts of HIV-related stigma on those directly impacted by it, a sense of understanding and compassion may be elicited through the breakdown of social stigma into comprehensible components and the provision of stigma-inspired artwork. In addition to providing a background on the scientific basis of Human immunodeficiency virus and its spread, the authors have elected to utilize public engagement by means of an anonymous survey as well as personal interactions with HIV advocates to synthesize paintings. Responses were collected from approximately 300 survey participants via social media with no demographic information collected. It was the hope of the authors that the lack of identifying questions may prompt participants to answer freely and honestly to improve overall understanding of social perceptions of HIV and its related stigma. These paintings and resources deemed appropriate based on the results of the aforementioned survey are to be displayed on a webpage for easier access and engagement with a broader audience.Moreover, this webpage is intended to be maintained and utilized beyond the timeframe of this Undergraduate Honors Thesis for the intended purpose of promoting stigma-free HIV advocacy and education.

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Date Created
  • 2018-05

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An Evaluation of HEAL International's Health Education Program in Tanzania, Africa

Description

This study investigated the potential efficacy of HEAL International's prevention education program in inducing health behavior change in HIV/AIDS, malaria, and communicable disease to children in grade levels ranging from

This study investigated the potential efficacy of HEAL International's prevention education program in inducing health behavior change in HIV/AIDS, malaria, and communicable disease to children in grade levels ranging from primary school to secondary school. The health education program was aimed at changing health behavior by increasing knowledge. This increase in knowledge was analyzed as a modifying factor in the Health Belief Model suggesting that knowledge, along with five other modifying factors, are directly responsible for an individual's health perceptions. These health perceptions ultimately result in an individual's health behavior. As a result, it is argued that an increase in knowledge can lead to health behavior change so long as it is coupled with a strong theoretical framework. Administering pre-evaluations at the beginning of the program, post evaluations at the end of the program, and a second post evaluation again two months later completed the evaluation. It was hypothesized that if there was a significant difference between the percent of correct answers at the pre-evaluation compared the second post-evaluation then there is evidence that HEAL's health education program is, or at least has the potential to, create sustainable health behavior change. A paired samples t-test was completed on the data and showed a statistically significant difference between the percent of correct answers at pre-evaluation and the percent of correct answers at second post-evaluation. These results indicated that the number of students with a comprehensive knowledge of the subjects that HEAL taught during the program had increased. It was concluded that the results of the study indicate evidence that HEAL's program has the potential to deliver sustainable health behavior change but that it will be more quantifiable once HEAL is able to adopt a theoretical framework on which to base future programs.

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Date Created
  • 2014-05

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Proposal to Institute a Needle Exchange in Maricopa County

Description

Utilizing a compilation of existing literature, theory and current praxis, a clear case for instituting a needle exchange in Maricopa County is visible.. Research on HIV rates are consulted to

Utilizing a compilation of existing literature, theory and current praxis, a clear case for instituting a needle exchange in Maricopa County is visible.. Research on HIV rates are consulted to establish a foundation for understanding the value of needle exchange programs nationally and in Maricopa County. Case studies on existing needle exchange efficacy are also used to support the proposal and outline the success of needle exchanges in reducing rates of infection.

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Date Created
  • 2013-05

STUDY OF INACTIVATION OF MS2 BACTERIOPHAGE BY ULTRA SHORT PULSES OF TI-SAPPHIRE LASER

Description

Studies have demonstrated that viruses such as human immunodeficiency virus [HIV], M13 bacteriophage, and murine cytomegalovirus [MCMV] have been effectively inactivated by exposure to ultra short-pulsed lasers (6,7,10,11,14,15,17). Ultra short

Studies have demonstrated that viruses such as human immunodeficiency virus [HIV], M13 bacteriophage, and murine cytomegalovirus [MCMV] have been effectively inactivated by exposure to ultra short-pulsed lasers (6,7,10,11,14,15,17). Ultra short pulse laser shows promise as a new method for non-invasive antiviral treatments (17). This method can be used to prevent problems such as drug resistance that is currently rising in numbers. According to the Center for Disease Control [CDC], there are more than two million people in the United States of America that are infected with antimicrobial-resistant infections and at least 23,000 deaths per year occur as a result (19). In this study, ultra-short pulses, specifically Ti-Sapphire Laser [USP Ti-Sapphire Laser] will be evaluated for viral inactivation. The virus chosen for this study was MS2 bacteriophage, which is a non- enveloped, icosahedral, single-stranded RNA [ssRNA] bacteriophages that infects F+ pilus Escherichia coli (16). It was hypothesized that ultrashort pulses from a Ti-Sapphire laser will inactivate MS2 bacteriophage. Inactivation was measured using plaque-forming units [PFU/mL] as an indicator. It was expected that there would be an increase in inactivation of MS2 bacteriophage with an increase in irradiation duration. The results indicated that MS2 bacteriophage was highly sensitive to irradiation treatments of the USP Ti-Sapphire Laser. The concentration of MS2 bacteriophage decreased by 107 PFU/mL after being treated for various time periods ranging from 5 minutes to 150 minutes. Longer duration of USP Ti- Sapphire Laser treatment inactivated more MS2 Bacteriophage.

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Created

Date Created
  • 2014-05