Saudi Cultural Missions Theses & Dissertations
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Item Restricted Analyzing the Spread of COVID-19 Misinformation on Twitter: Patterns, Impact, and Countermeasures(Auckland University of Technology, 2024) Abokhanjar, Hissah; Li, Weihua; Wang, XiaodanTwitter, as a significant information hub during the pandemic, has facilitated the rapid spread of accurate updates and false narratives, contributing to the ‘infodemic.’ This study investigates the most common types of COVID-19 misinformation spread on Twitter and examines their impact on public perception and behavior. By analyzing a substantial dataset of COVID-19-related tweets, the research identifies recurring misinformation themes, including erroneous claims about the virus’s origin, prevention strategies, treatments, and vaccine efficacy. Prominent misinformation types include theories falsely attributing the virus’s origin to human engineering or intentional release, unproven prevention methods like natural remedies, and misleading treatment options, such as the promotion of unapproved drugs. Additionally, vaccine-related misinformation, including baseless claims about vaccine safety, side effects, and hidden agendas, contributed significantly to public skepticism and hesitancy. The study explores how these misinformation narratives influenced public attitudes and behaviors, revealing that exposure led to increased vaccine hesitancy, reduced compliance with public health guidelines, and the widespread acceptance of conspiracy theories. These effects complicated public health efforts and deepened social and political divisions, further impeding effective pandemic management. The findings highlight the urgent need for strategies to counter misinformation and promote accurate public health information, especially during global crises. Public health authorities, social media platforms, and educators must collaborate to enhance information literacy, improve content moderation, and develop targeted interventions. These efforts are crucial to mitigating the spread and impact of misinformation, thereby safeguarding public health and trust in scientific expertise.22 0Item Restricted Development of flexible hepatitis B virus core protein virus-like particles as a universal vaccine scaffold using a range of antigen-capturing systems(University of Leeds, 2024-07) Alzahrani, Jehad Abdulaziz; Stonehouse, Nicola; Stacey, MartinThe development of safe and flexible vaccines is an essential tool to fight emerging and re-emerging pathogens. Virus-like particles (VLPs) offer promising and adaptable options in vaccine development due to their safety and high immunogenicity. VLPs are non-infectious viral structures mimicking native viruses and can stimulate cellular and humoral immune responses. Additionally, VLPs can be modified as generic vaccine platforms to present various antigens. In this project, hepatitis B core antigen (HBcAg) VLPs were investigated as a presentation platform based on a fused dimer of two monomeric subunits. HBcAg VLPs were modified to incorporate antigen-capturing systems (ACSs) to create a new platform. The ACSs used here are small artificial non-antibody binding proteins that recognise and bind specific protein targets. The ACSs selected were an Affimer against small ubiquitin-like modifier (SUMO) tag, as well as the SpyTag/SpyCatcher systems. In model one, VLPs presented a single ACS: Affimer, SpyTag, or SpyCatcher at the N-terminus or the major immunodominant region (MIR) of HBcAg. In model two, dual antigen-capturing systems (dACSs) were used: Affimer was engineered into the MIR and SpyTag into the N-terminus. The dACS VLPs allow the decoration with dual antigens to enhance immunogenicity against a specific pathogen. These VLPs were successfully produced in a yeast expression system (Pichia pastoris, which is also known as Komagataella phaffii). In addition to the production of different VLPs, a fragment of glycoprotein G from respiratory syncytial virus (RSV-G) was also generated. The RSV-G protein was tagged with either SUMO tag or SpyCatcher to allow interaction with the corresponding VLP. RSV-G proteins were then successfully expressed in mammalian expression systems. The VLPs described above were decorated with a range of proteins, including glycoprotein 1 (GP1) of the Junín virus and glycoprotein G of the RSV-G. One of the VLPs was tested in an immunisation study in mice (with Junín virus GP1 as an antigen). The results showed superior responses for the decorated VLPs compared to the noncomplexed GP1. The results described in this thesis have demonstrated the development of a novel vaccine platform that could be employed with a number of different antigens in the future.24 0Item Restricted Intracellular and extracellular immunisation for HIV(The University of Manchester, 2024-11) Alatiq, Abdulrahman; Klapper, Paul; Valley, Pamela; Faqih, LaylaThe prevalence of HIV infection remains a serious challenge for public health. HIV infection results in considerable mortality and morbidity, as well as imposing a substantial financial burden on healthcare systems globally. Despite the availability of effective antiretroviral treatments to control infection, an effective protective vaccine remains elusive. This project aimed to develop a practical, affordable, and effective combined vaccine and treatment by combining intracellular antibodies and extracellular immunisation to prevent or reduce HIV viraemia. Specifically, an approach in which DNA-encoding N49P7 broadly neutralising antibodies against the HIV-1 envelope glycoprotein 120 is delivered to cells using recombinant baculovirus or lipid nanoparticle (LNP) transfection. Extracellular antibodies were anticipated to prevent gp120 from attaching to cells, and intracellular antibodies were intended to inhibit the genesis of virions. The expression of N49P7, either as a human IgG antibody or as human Fab, was attempted. The expression of the N49P7 IgG antibody was not achieved in HEK 293 cells despite employing three delivery models for transfections: recombinant baculovirus, MC3-based LNP, or lipofectamine 2000 LNP. While transfection was successfully achieved (monitored via an eGFP gene included within the plasmid design), functional antibody was not achieved. The most likely explanation for the failure was thought to be the use of dual promoters within the expression cassette. Redesign of the plasmid to create a bicistronic vector including the N49P7 Fab region and signal peptide sequences of murine IgG and IL-2 allowed successful expression of N49P7 Fab through recombinant baculovirus or lipofectamine 2000 reagent transfection of HEK 293 cells. However, the expressed N49P7 Fab region was predominantly accumulated intracellularly. A further redesign was implemented to incorporate homogenous signal peptides H7 and L1 into the N49P7 Fab gene, which significantly enhanced the secretion of the antibody fragment. This design maintained functional intracellular and extracellular antibody activity. Lower cellular cytotoxicity was seen with recombinant baculovirus transfection compared to lipofectamine 2000 LNP mediated transfection although both were equally efficient. The selection of an optimum method for transfection will form part of future investigations progressing to animal model testing. This proof of principle study showed that recombinant baculovirus or lipofectamine 2000-mediated transfection systems allowed efficient N49P7 Fab expression both intracellularly and extracellularly in mammalian cells, suggesting that this approach indicates potential for providing a vaccine against HIV infection in addition to a therapeutic intervention for those who already have HIV infection.12 0Item Restricted The Development of a Synthetic Self-Adjuvanting Cancer Vaccine(Saudi Digital Library, 2023-10-26) Aljohani, Salwa; Mitchell, NicholasCancer testis antigens (CTA) have demonstrated high immunogenicity towards multiple cancer types, and due to their restricted expression profile, they warrant further attention as potential vaccine candidates. Covalently attaching an adjuvant to an antigen is an effective strategy to induce a strong, targeted immune response. This thesis describes a robust synthetic method to palmitoylate CTA peptides with a di-palmitoyl-S-glyceryl cysteine residue (Pam2Cys). These adjuvants, known to effectively enhance the severity of an immune response, were covalently linked to the chosen CTA sequences to develop a self-adjuvanting, targeted cancer vaccine. Liposomes can provide adjuvant activity either by enhancing antigen delivery or by activating innate immune responses. To examine this, a CTA antigen bearing an N-terminal Cys was conjugated covalently to the outer envelope of liposome particles via conjugation to a lipid carrying an appropriate electrophilic headgroup. The palmitoylated CTA sequences with native Pam2Cys were also inserted into the lipid bilayer of the liposomes via the palmityl 'tails' and these strategies of adjuvant and antigen incorporation into the particle formulation compared. The immune responses generated by the self-adjuvanting CTA peptide vaccine constructs, self-adjuvanting CTA peptides formulated into liposomal vaccine formulations, and the liposomes carrying the conjugated peptide antigens onto outer envelope of the nanoparticles were examined in vivo using healthy mouse models.23 0Item Restricted Optimizing the Selection of COVID-19 Vaccine Distribution Centers and Allocation Quantities: A Case Study for the County of Los Angeles(2023-07) Aljohani, Basim; Hall, RandolphThis thesis aims to provide a tool to help policy and decision-makers establish well-informed plans about the selection and distribution of locations and quantities of vaccines. Optimization of vaccine distribution centers' locations plays a crucial role in providing communities with easy access to vaccines, which will help in controlling global pandemics, such as the recent COVID-19, and mitigate the risks of losing lives and economic losses. As studies have proven, strategic planning of the vaccine site locations and the allocated quantities of the vaccines could help boost the amount of vaccine uptake. This thesis utilizes mathematical modeling techniques to develop a mixed integer program that aims to minimize travel time, distance, and associated costs in one of the largest counties in the United States, Los Angeles County. The developed model takes into account the diverse demographics and socioeconomic factors of the County and plans for the selection and allocations accordingly. The model explores 277 zip codes within Los Angeles and analyzes them as potential vaccine distribution centers. It also incorporates the two different and most common means of transportation, cars, and public transit, to account for all users. Three scenarios are explored where each zip code of the 277 is assigned priority based on the following factors: population, Healthy Places Index, and a Vulnerability to COVID-19 index. The output showed significant improvements in reducing average travel times and distances as well as savings in costs when compared to the actual selected sites within the County.15 0