Saudi Cultural Missions Theses & Dissertations
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Item Restricted The role of pneumococcal protein antigens in immune cell stimulation and novel vaccine delivery methods for immunisation(University of Liverpool, 2024) Alshuhaytan, Tarfah Abdulrahman; Kadioglu, ArasStreptococcus pneumoniae remains one of the most deadly pathogens worldwide, causing pneumonia, sepsis and meningitis, as well as significant morbidity and mortality. This study examines the virulence and host immune cell responses to three pneumococcal strains: serotype two (D39) and its pneumolysin-negative isogenic mutant (D39Ply-/-), and highly invasive serotype one strain (ST217). Immune responses were examined in vitro against these three strains using THP1-derived macrophage and dendritic cells at diVerent time points. Notably, significant variations were observed in growth patterns, hemolytic activity, and capsule thickness among these diVerent pneumococcal strains. Importantly, the toxin pneumolysin and capsule thickness were key factors influencing the pathogenicity and virulence of ST217. Another major aspect of my work was the identification of potential vaccine candidates. To achieve this, I examined the immunogenic components of pneumococcal cell culture supernatant (CCS) from D39, D39Ply-/-, and ST217 by incubating the CCS with antigen-presenting cells such as macrophages and dendritic cells in-vitro and identifying the proteins using a mass-spectrometry approach.102 0Item Restricted Immunity and protection induced by outer membrane vesicles against Invasive non-Typhoidal Salmonella(University of Birmingham, 2024-05-24) Alshayea, Areej; Cunningham, AdamSalmonella enterica is responsible for causing both diarrheal and systemic illnesses, which remain significant global concerns. The development of vaccines that offer broad protection against multiple serovars holds potential in effectively managing diseases caused by Salmonella. Outer Membrane Vesicles (OMVs), which are naturally released by Gram-negative bacteria, show promising potential for developing subunit vaccines due to their high immunogenicity and protective effectiveness. The O-antigen of lipopolysaccharide (LPS) has been identified as a key target for inducing protective immunity. However, variation in O-antigen expression between closely related pathogens, such as S. Typhimurium and S. Enteritidis, limits cross-protection after natural infection. Modifications in the O-antigen chain length can alter outer membrane structure and composition. In this study, genetic mutations were introduced into Salmonella OMV-producing strains in order to reduce or delete LPS O-antigen expressions. The cellular, humoral, and functional immune responses to OMV from S. Typhimurium expressing wild-type length O-antigens (WT-OMV), ≤1 O-antigen repeat (wzy-OMV), or no O-antigen (wbaP-OMV) were assessed in mice immunisation studies. All OMV induced similar plasma cell and germinal centre responses, although the nature and outcomes of these responses differed. Surprisingly, wzy-OMV elicited comparable levels of anti-LPS IgG responses to WT-OMV. However, wzy-OMV and wbaP-OMV induced more robust responses against cell-surface-exposed porin proteins and cross-reactive antibodies targeting S. Enteritidis. Immunisation with wzy-OMV provided protection against S. Typhimurium comparable to that induced by WT-OMV. In contrast, after one immunisation, with any OMV type, there was minimal control of S. Enteritidis infections, except in the blood. However, after boosting with OMVs, there was an enhanced level of cross-protection.4 0Item Restricted ASSOCIATION BETWEEN PARENTS’ PERCEPTIONS ABOUT HUMAN PAPILLOMAVIRUS (HPV) AND CORONAVIRUS DISEASE-19 (COVID-19) VACCINES AND THEIR DECISION TO VACCINATE THEIR CHILD AGAINST HPV(2023) Almatruk, Ziyad; Axon, David R; Warholak, TerriBACKGROUND: The WHO classified vaccine hesitancy as one of the top ten threats to global health. During the COVID-19 pandemic, many people had doubt about vaccines. The HPV can lead to several types of cancer. The COVID-19 impact on US HPV vaccination reluctance is unknown. Thus, the aim of the study is to investigate parents' perceptions of Coronavirus Disease-19 (COVID-19), the Human Papillomavirus (HPV) vaccine, and HPV vaccination decisions. METHODS: A cross-sectional observational survey was administered using Qualtrics to United States parents with at least one child aged 9–18. The survey consisted of five sections: screening, parent’s perception of general Vaccination, COVID-19, HPV, and demographics. Rasch analysis was used to evaluate the instrument reliability and validity, which included principal component analysis (PCA), scale functionality, person measure, item reliability, and person reliability. A logistic regression model with variables selected using backward elimination (p<0.05) was used to evaluate the associations between parents’ perception of COVID-19 and HPV vaccine decisions. RESULTS: The study included 508 parents. The instrument contained four domains: General Vaccination, COVID-19, HPV, and Parents’ COVID-19 Experience. Except for General Vaccination, PCA showed unidimensionality. Response options satisfied scale functionality analysis. Average person measure was 0.7±8.0 logits. Person reliability was 0.7-0.9, whereas item reliability was 0.9-1.0. Item fit ranged from 0.7-2.1. A few of the difficult items to endorse with were I trust social media and/or TV to tell me the truth about vaccines, I would have my 11 children vaccinated for COVID-19 if their school required it, vaccinating my child against HPV helps to protect others from getting HPV, and I believe the COVID-19 vaccine was approved in a reasonable amount of time. A few of the easy items to endorse were physicians’ address vaccine concerns, there are safe COVID-19 vaccines for children, and I believe in vaccines. The multivariate logistic regression model with backward elimination showed that HPV Domain (adjusted odds ratio [AOR] = 1.89, 95% CI = 1.61 – 2.21), Parents COVID-19 Experience Domain (AOR = 1.32, 95% CI = 1.18 – 1.47), and men compared to women (AOR = 2.48, 95% CI = 1.37 – 4.47) were significantly associated with parents’ planning not to vaccinate their children with HPV. CONCLUSIONS: Our research offers insight into variables associated with parents’ decisions about children’s COVID-19 and HPV vaccines. More research is needed to improve the HPV vaccine uptake.7 0