Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKat... more Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKatrina. Abstract. Thesis (Ph. D.)--University of Queensland, 1995.. Includes bibliography. Details der Publikation. Download, http://worldcat.org/oclc/37404118. ...
The aim of the project was to evaluate mechanisms of vaccine-induced protection against Helicobac... more The aim of the project was to evaluate mechanisms of vaccine-induced protection against Helicobacter pylori infection in mice. In particular, to elucidate the role of cytokines induced by H. pylori infection in promoting the protective or pathogenic immune responses in the stomach. Our group has previously shown that sublingual (SL; under the tongue) vaccination with H. pylori antigens and cholera toxin as an adjuvant was efficient in reducing the bacterial load in the stomach of mice with enhanced IFNγ and IL-17A responses in the stomach compared to unvaccinated mice. Using gene knockout mice and neutralizing antibodies, the impact of cytokines IFNγ and IL-17A on the bacterial load, immune responses and gastric inflammation was addressed. We report that after SL vaccination, IFNγ gene knockout (IFNγ−/−) mice were protected against H. pylori infection and had elevated IL-17A production and lower inflammation scores in the stomach compared to vaccinated wild-type mice. Furthermore, i...
There is a growing demand for better delivery systems to improve the stability and efficacy of DN... more There is a growing demand for better delivery systems to improve the stability and efficacy of DNA vaccines. Here we report the synthesis of a non-viral DNA vaccine delivery system using a novel adjuvanted solid lipid nanoparticle (SLN-A) platform as a carrier for a DNA vaccine candidate encoding the Urease alpha (UreA) antigen from Helicobacter pylori. Cationic SLN-A particles containing monophosphoryl lipid A (adjuvant) were synthesised by a modified solvent-emulsification method and were investigated for their morphology, zeta potential and in vitro transfection capacity. Particles were found to bind plasmid DNA to form lipoplexes, which were characterised by electron microscopy, dynamic light scattering and fluorescence microscopy. Cellular uptake studies confirmed particle uptake within 3 h, and intracellular localisation within endosomal compartments. In vitro studies further confirmed the ability of SLN-A particles to stimulate expression of pro-inflammatory cytokine tumor ne...
Advances in Experimental Medicine and Biology, 2019
Helicobacter pylori is a highly-adapted gastrointestinal pathogen of humans and the immunology of... more Helicobacter pylori is a highly-adapted gastrointestinal pathogen of humans and the immunology of this chronic infection is extremely complex. Despite the availability of antibiotic therapy, the global incidence of H. pylori infection remains high, particularly in low to middle-income nations. Failure of therapy and the spread of antibiotic resistance among the bacteria are significant problems and provide impetus for the development of new therapies and vaccines to treat or prevent gastric ulcer, and gastric carcinoma. The expansion of knowledge on gastric conventional and regulatory T cell responses, and the role of TH17 in chronic gastritis from studies in mouse models and patients have provided valuable insights into how gastritis is initiated and maintained. The development of human challenge models for testing candidate vaccines has meant a unique opportunity to study acute infection, but the field of vaccine development has not progressed as rapidly as anticipated. One clear lesson learned from previous studies is that we need a better understanding of the immune suppressive mechanisms in vivo to be able to design vaccine strategies. There is still an urgent need to identify practical surrogate markers of protection that could be deployed in future field vaccine trials. Important developments in our understanding of the chronic inflammatory response, progress and problems arising from human studies, and an outlook for the future of clinical vaccine trials will be discussed.
Advances in experimental medicine and biology, 2016
Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing... more Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission.Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imagin...
The trefoil factor TFF2 is a member of a tripartite family of small proteins that is produced by ... more The trefoil factor TFF2 is a member of a tripartite family of small proteins that is produced by the stomach and the colon. Recombinant TFF2, when applied intrarectally in a rodent model of hapten colitis, hastens mucosal healing and reduces inflammatory indexes. Additionally, TFF2 is expressed in immune organs, supporting a potential immunomodulatory and reparative role in the bowel. In this study we confirm that TFF2 is expressed in the colon and is specifically enriched in epithelial cells relative to colonic leukocytes. TFF2-deficient, but not TFF1-deficient, mice exhibit a more severe response to acute or chronic dextran sulfate (DSS)-induced colitis that correlates with a 50% loss of expression of TFF3, the principal colonic trefoil. In addition, the response to acute colitis is associated with altered expression of IL-6 and IL-33, but not other inflammatory cytokines. While TFF2 can reduce macrophage responsiveness and block inflammatory cell recruitment to the colon, the maj...
Proceedings of the National Academy of Sciences, 1996
Live vaccine vectors are usually very effective and generally elicit immune responses of higher m... more Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gut-associated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wild-type strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the reco...
Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKat... more Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKatrina. Abstract. Thesis (Ph. D.)--University of Queensland, 1995.. Includes bibliography. Details der Publikation. Download, http://worldcat.org/oclc/37404118. ...
Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKat... more Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKatrina. Abstract. Thesis (Ph. D.)--University of Queensland, 1995.. Includes bibliography. Details der Publikation. Download, http://worldcat.org/oclc/37404118. ...
The effect of antigen delivery profiles on antibody responses were studied by administering bovin... more The effect of antigen delivery profiles on antibody responses were studied by administering bovine serum albumin (BSA) to mice in various delivery profiles; continuously from mini-osmotic pumps, by injection or combinations of pumps and injections. The level and relative avidity of antibody responses were monitored for up to 40 weeks by ELISA. Continuous delivery of BSA stimulated equivalent levels of antibody to delivery by injections over the same time periods (4, 8 or 12 weeks). Administration of part of the antigen dose as an injection either before or after continuous delivery increased antibody levels for only a transient period compared to other treatments. The time period between injections of BSA significantly affected the levels of antibody induced.
Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKat... more Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKatrina. Abstract. Thesis (Ph. D.)--University of Queensland, 1995.. Includes bibliography. Details der Publikation. Download, http://worldcat.org/oclc/37404118. ...
The aim of the project was to evaluate mechanisms of vaccine-induced protection against Helicobac... more The aim of the project was to evaluate mechanisms of vaccine-induced protection against Helicobacter pylori infection in mice. In particular, to elucidate the role of cytokines induced by H. pylori infection in promoting the protective or pathogenic immune responses in the stomach. Our group has previously shown that sublingual (SL; under the tongue) vaccination with H. pylori antigens and cholera toxin as an adjuvant was efficient in reducing the bacterial load in the stomach of mice with enhanced IFNγ and IL-17A responses in the stomach compared to unvaccinated mice. Using gene knockout mice and neutralizing antibodies, the impact of cytokines IFNγ and IL-17A on the bacterial load, immune responses and gastric inflammation was addressed. We report that after SL vaccination, IFNγ gene knockout (IFNγ−/−) mice were protected against H. pylori infection and had elevated IL-17A production and lower inflammation scores in the stomach compared to vaccinated wild-type mice. Furthermore, i...
There is a growing demand for better delivery systems to improve the stability and efficacy of DN... more There is a growing demand for better delivery systems to improve the stability and efficacy of DNA vaccines. Here we report the synthesis of a non-viral DNA vaccine delivery system using a novel adjuvanted solid lipid nanoparticle (SLN-A) platform as a carrier for a DNA vaccine candidate encoding the Urease alpha (UreA) antigen from Helicobacter pylori. Cationic SLN-A particles containing monophosphoryl lipid A (adjuvant) were synthesised by a modified solvent-emulsification method and were investigated for their morphology, zeta potential and in vitro transfection capacity. Particles were found to bind plasmid DNA to form lipoplexes, which were characterised by electron microscopy, dynamic light scattering and fluorescence microscopy. Cellular uptake studies confirmed particle uptake within 3 h, and intracellular localisation within endosomal compartments. In vitro studies further confirmed the ability of SLN-A particles to stimulate expression of pro-inflammatory cytokine tumor ne...
Advances in Experimental Medicine and Biology, 2019
Helicobacter pylori is a highly-adapted gastrointestinal pathogen of humans and the immunology of... more Helicobacter pylori is a highly-adapted gastrointestinal pathogen of humans and the immunology of this chronic infection is extremely complex. Despite the availability of antibiotic therapy, the global incidence of H. pylori infection remains high, particularly in low to middle-income nations. Failure of therapy and the spread of antibiotic resistance among the bacteria are significant problems and provide impetus for the development of new therapies and vaccines to treat or prevent gastric ulcer, and gastric carcinoma. The expansion of knowledge on gastric conventional and regulatory T cell responses, and the role of TH17 in chronic gastritis from studies in mouse models and patients have provided valuable insights into how gastritis is initiated and maintained. The development of human challenge models for testing candidate vaccines has meant a unique opportunity to study acute infection, but the field of vaccine development has not progressed as rapidly as anticipated. One clear lesson learned from previous studies is that we need a better understanding of the immune suppressive mechanisms in vivo to be able to design vaccine strategies. There is still an urgent need to identify practical surrogate markers of protection that could be deployed in future field vaccine trials. Important developments in our understanding of the chronic inflammatory response, progress and problems arising from human studies, and an outlook for the future of clinical vaccine trials will be discussed.
Advances in experimental medicine and biology, 2016
Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing... more Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission.Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imagin...
The trefoil factor TFF2 is a member of a tripartite family of small proteins that is produced by ... more The trefoil factor TFF2 is a member of a tripartite family of small proteins that is produced by the stomach and the colon. Recombinant TFF2, when applied intrarectally in a rodent model of hapten colitis, hastens mucosal healing and reduces inflammatory indexes. Additionally, TFF2 is expressed in immune organs, supporting a potential immunomodulatory and reparative role in the bowel. In this study we confirm that TFF2 is expressed in the colon and is specifically enriched in epithelial cells relative to colonic leukocytes. TFF2-deficient, but not TFF1-deficient, mice exhibit a more severe response to acute or chronic dextran sulfate (DSS)-induced colitis that correlates with a 50% loss of expression of TFF3, the principal colonic trefoil. In addition, the response to acute colitis is associated with altered expression of IL-6 and IL-33, but not other inflammatory cytokines. While TFF2 can reduce macrophage responsiveness and block inflammatory cell recruitment to the colon, the maj...
Proceedings of the National Academy of Sciences, 1996
Live vaccine vectors are usually very effective and generally elicit immune responses of higher m... more Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gut-associated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wild-type strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the reco...
Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKat... more Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKatrina. Abstract. Thesis (Ph. D.)--University of Queensland, 1995.. Includes bibliography. Details der Publikation. Download, http://worldcat.org/oclc/37404118. ...
Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKat... more Publikationsansicht. 5849738. The delivery of antigens for vaccination / (1995). Walduck, AnnaKatrina. Abstract. Thesis (Ph. D.)--University of Queensland, 1995.. Includes bibliography. Details der Publikation. Download, http://worldcat.org/oclc/37404118. ...
The effect of antigen delivery profiles on antibody responses were studied by administering bovin... more The effect of antigen delivery profiles on antibody responses were studied by administering bovine serum albumin (BSA) to mice in various delivery profiles; continuously from mini-osmotic pumps, by injection or combinations of pumps and injections. The level and relative avidity of antibody responses were monitored for up to 40 weeks by ELISA. Continuous delivery of BSA stimulated equivalent levels of antibody to delivery by injections over the same time periods (4, 8 or 12 weeks). Administration of part of the antigen dose as an injection either before or after continuous delivery increased antibody levels for only a transient period compared to other treatments. The time period between injections of BSA significantly affected the levels of antibody induced.
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