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Dissertations / Theses on the topic 'Vaccines'
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1
Farfan, Arribas Diego Jose. "DNA Vaccines Against HIV-1: Augmenting Immunogenicity of gp120." Link to electronic thesis, 2002. http://www.wpi.edu/Pubs/ETD/Available/etd-0107102-160706/.
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Parker, Christopher S. "Effect of a codon optimized DNA prime on induction of anti-influenza protective antibodies." Worcester, Mass. : Worcester Polytechnic Institute, 2007. http://www.wpi.edu/Pubs/ETD/Available/etd-040907-100839/.
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Satti, Iman. "Immunogenicity of anti-leishmaniasis vaccines in man /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-779-7/.
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Rainczuk, Adam 1976. "Evaluation of DNA vaccine targeting strategies and expression library immunisation against lethal erythrocytic stage Malaria." Monash University, Dept. of Biochemistry and Molecular Biology, 2003. http://arrow.monash.edu.au/hdl/1959.1/5685.
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Grubb, Kimberley L. "A genomic approach to the identification of novel malaria vaccine antigens /." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98715.
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As the number of drug-resistant malaria parasites continues to grow, pressure is increasing to find an effective, cross-protective, multi-valent malaria vaccine (32). Expression library immunisation is an un-biased screening technique that leads to the identification of novel, protective antigens that can be administered as components of a multivalent DNA vaccine (9, 50, 75, 86, 92). Here, a P. c. adami DS expression library has been evaluated as a malaria vaccine in mice, and several subpools of cross-protective plasmids have been identified. Upon vaccination with these plasmid subpools, mice demonstrate significantly lower mean cumulative parasitemia values than control vaccinated mice, when challenged with avirulent heterologous P. c. adami DK parasites. These cross-protective responses correlate with the induction of opsonizing antibodies against infected red blood cells and the production of IFN-gamma by T-cells. The determination of P. c. adami antigens capable of inducing strain-transcending immunity implies the identification of orthologues in the P. falciparum genome that may be applied as components of a human malaria vaccine.
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Atcheson, Erwan. "Prospects for enhancing malaria vaccine efficacy by combining pre-erythrocytic antigens." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:6506c003-7065-4d48-b049-f5e9136443d5.
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Malaria causes almost half a million deaths each year. Existing interventions will almost certainly not be enough to tackle this enormous public health problem on their own. An effective vaccine is urgently needed. The leading malaria vaccine, RTS,S, confers suboptimal protective efficacy, and in addition targets only Plasmodium falciparum and not the other major species of human malaria, P. vivax. This thesis investigates the potential of combining pre-erythrocytic malaria vaccines as a means of enhancing protective efficacy. A novel mathematical model was developed which expresses probability of protection as a function of vaccine-induced humoural and cellular responses. The model predicts that combining partially effective vaccines should result in more than additive improvements in protective efficacy. This was supported by an experiment combining Rv21, a P. vivax circumsporozoite virus-like particle, with viral vectored P. vivax TRAP, the two leading pre-erythrocytic malaria vaccine antigens; this combination raised protective efficacy from 50% and 0%, respectively, to 100% sterile protection. It was also found that antigenic interference, a reduction in anti-CSP titres when Rv21 and PvTRAP are combined, occurred only in the presence of Matrix M adjuvant, and not when using alum, AddaVax or no adjuvant. With a view to creating a single-component multi-antigen vaccine, which would be more cost-effective than a multi-component vaccine, experiments were carried out to establish the virus-like particle Qβ as a platform capable of eliciting protective immunity via the display of short peptides derived from the CSP repeat region of both P. vivax and P. falciparum. For the first time, a tetramer peptide derived from the CSP repeat region of P. vivax VK210, AGDR, was shown capable of eliciting protective immunity alone. Finally, five novel linear B-cell epitopes were discovered, one from P. falciparum CSP, three from P. vivax TRAP and one from TRSP, each capable of conferring partial protection on mice. These epitopes were identified using novel screening methods, using sera from whole-protein vaccinated mice or by exploiting conservation within invasion protein sequences. Two of the protective epitopes, (NANP)6 and (ADGN long) were combined and found to enhance protective efficacy as predicted by the mathematical model. Thus this thesis lays the groundwork for the development of a single-component multi-epitope malaria vaccine with enhanced protective efficacy.
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Hutchings, Claire L. "Combination vaccines." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437038.
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Singh, Gagandeep. "RNA Viral Prophylaxis: Problems and Potential Solutions." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29458.
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Over 80% of the newly emerging infectious diseases are caused by RNA viruses. Major global problems associated with the development of vaccines against the RNA virus are their high genetic and antigenic diversity. Hence, effective control of epidemics with newly emerging RNA viruses require improved vaccines which are either specific to the new strain or broadly effective even when new viral strains emerge. The main focus of this dissertation is to develop epidemic vaccines using these two approaches. Using a newly emerged swine enteric virus called porcine epidemic diarrhea virus (PEDV) as a model, our first goal was to develop a quick and easy method for rapid response vaccines with potential applicability to a range of RNA viruses. We hypothesized that the methods which can disrupt genomic RNA without impacting the structural integrity of the virus would result in attenuated vaccine with minimum replication in the host while inducing immune responses. As hypothesized, developed rapid response PEDV vaccine induced complete protection against the virulent challenge virus, while vaccine viral shedding was not detected in vaccinated pigs. To address the second problem of rapid viral evolution leading to vaccines becoming obsolete, we used swine influenza virus (SIV) as a model to develop and test a universal vaccine composed of peptides encoding conserved antigenic epitopes which are present in most influenza A viruses. Importantly, a novel amphiphilic invertible polymer (AIP) was used to address the well-recognized problem of poor antigenicity of peptides. We hypothesized that peptides encoding conserved epitopes when conjugated with an AIP will induce strong immune responses and protect against challenge virus. While the conserved epitopes were previously tested by others in mice, we were the first to test a combination of these epitopes in pigs. Pigs vaccinated with the peptide polymer vaccine mounted strong antibody responses against the epitopes indicating that the delivery system was effective. However, protection against replication of the challenge virus was delayed. In summary, the methods developed and tested in this body of work significantly contribute to the area of emergency response management in infectious disease outbreaks.United States Department of Agriculture, National Institute of Food and Agriculture (USDA-NIFA)
North Dakota State Agricultural Products Utilization Committee (ND APUC)
North Dakota State Board of Agricultural Research (ND SABRE)
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Khan, Tila. "Tailored influenza virus vaccines for both the young and old: Vaccine Efficacy of Whole Inactivated Vaccines bearing Immunomodulatory Adjuvants or Multimeric peptides." Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/77130.
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Influenza epidemics and pandemics remain a significant burden to world health and economy. Low efficacy of current inactivated influenza vaccines in the elderly and immunocompromized and the inability to protect against antigenically drifted or shifted strains of influenza virus are the two major problems in influenza vaccine research. To overcome these hurdles, we have utilized an in vitro cell culture vaccine platform, which results in whole inactivated influenza vaccine (WIV) bearing bioactive membrane-anchored immunomodulatory proteins such as cytokines on the virion surface, collectively known as CYT-IVACs (Cytokine bearing-Inactivated Vaccine). In addition, we tested whether a multimeric M2e peptide presented on WIV can serve to enhance immunogenicity and augment protective efficacy of whole virus vaccines. Our panel of cytokines includes IL-2, IL-4, IL-12, IL-23, and Flt3L as well as the multimeric M2e peptide, all fused to the membrane anchoring regions of influenza virus hemagglutinin protein and constitutively expressed in virus permissive MDCK cell line. Subsequent infection with influenza virus results in incorporation of fusion constructs directly into budding progeny virions that are harvested, purified and inactivated to generate distinct CYT-IVAC formulations. Following validation of immunomodulator incorporation, vaccines were tested for in vivo efficacy in either "young adult" or "aged" female Balb/c mice. Our results demonstrate that our CYT-IVAC~IL-12/HA and CYT-IVAC~IL-23/HA serve as potent mucosal adjuvants in young adult mice elicited significantly high levels of mucosal IgA antibodies and afford superior protection against lethal virus challenge. Our Flt3L/HA formulation was the most effective stimulator of systemic anti-viral antibody levels. In "aged" mice a single dose formulation of IL-12 bearing CYTIVAC was superior at affording protection against lethal homotypic virus challenge. Finally, administration of multimeric M2e molecule co-presented on WIV elicited prolonged antibody responses in "young adult mice" and provided cross-protection from challenge with the heterologous influenza A pandemic strain 2009 H1N1. In conclusion, the CYT-IVAC approach represents a novel tailored advancement to current WIV approaches that has the potential to elicit both potent mucosal and systemic immune responses in young and old.Ph. D.
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Dannetun, Eva. "Reasons for non-vaccination /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-739-1/.
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Zhang, Yaobi. "Schistosoma japonicum : studies on defined antigen vaccines and irradiated vaccines." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285204.
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Dunachie, Susanna Jane. "Malaria vaccines and microarrays : clinical and laboratory evaluation of two vaccine regimens." Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446277.
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Bernocchi, Beatrice. "Porous maltodextrin nanoparticles for the intranasal delivery of vaccines." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S010/document.
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Au cours des dernières décennies, la technologie des nanoparticules pour la délivrance des vaccins au niveau de muqueuses a reçu un intérêt croissant. L’administration intranasale possède de grands avantages pour la stimulation du système immunitaire, telles que la stimulation d’une immunité protectrice locale et systémique. Cependant des systèmes de délivrance et des adjuvants sont souvent nécessaires pour déclencher efficacement la réponse immunitaire. Nous avons appliqué la technologie des nanoparticules en tant que système de délivrance d'un vaccin universel nasal contre la grippe dans un projet européen FP7 appelé UniVacFlu. Nous avons formulé un antigène adjuvé CTA1-3M2e-DD avec les NPL. Cet antigène est composé de la sous-unité A1 de la toxine du choléra et d’un épitope conservé du virus de la grippe A (M2e), ainsi que du dimère de l’analogue synthétique de la protéine A de Staphylococcus aureus (DD). Les nanoparticules utilisées sont poreuses et constituées de maltodextrines réticulées ayant un coeur lipidique (NPL). L’association de cet antigène avec les NPL est quantitative et la formulation est stable pendant au moins six mois à 4°C. Les NPL permettent également de délivrer d’une manière accrue cet antigène dans les cellules épithéliales des voies respiratoires et les macrophages. Actuellement ces formulations sont évaluées chez la souris par le consortium UniVacFlu.L'un des principaux problèmes des vaccins nasal est la toxicité qui peut être provoquée par le passage nez-cerveau de l'un de ses composants. Le but de ce travail est d'évaluer le potentiel des NPL, en tant que vecteurs pour la délivrance des vaccins nasal. Ainsi, nous avons étudié le chargement d’un antigène dans les NPL et sa délivrance dans les cellules épithéliales des voies respiratoires. Notre étude révèle que les NPL interagissent fortement avec les muqueuses et délivrent d’une manière accrue les antigènes dans les cellules. Nous avons également montré l'absence de transcytose et de passage paracellulaire des NPL ou des antigènes délivrés dans un modèle de barrière épithéliale in vitro. Les résultats in vivo confirment l'absence de passage nez-cerveau des NPL et montrent qu’elles prolongent fortement le temps de résidence nasale des antigènes qui sont ensuite éliminés par le tractus gastro-intestinal.Ces résultats mettent en évidence l'intérêt des NPL comme vecteurs pour la prochaine génération de médicaments et de vaccinsNanoparticles technology for mucosal delivery of vaccines received a growing interest in the last decades. Intranasal administration owns great advantages for immune system stimulation, such as local and systemic protection against infectious diseases. However delivery systems and adjuvants are often required to efficiently trigger mucosal and systemic immune responses. In this thesis, nanoparticles (NP) have been evaluated as delivery system for a nasal universal influenza vaccine in a People Program of the European Union Seventh Framework Program FP7 called UniVacFlu. The aim of the UniVacFlu network is to develop a universal influenza vaccine administered through the mucosal route. We used porous maltodextrin nanoparticles with a lipidic core (NPL). We loaded an adjuvanted antigen named CTA1-3M2e-DD in the NPL. CTA1-3M2e-DD is composed of the A1 subunit of the cholera toxin and a conserved epitope of influenza A virus (M2e), while DD, dimer of the synthetic analogue of the Staphyloccous aureus protein A, targets B cells. Interestingly the antigen loading in NPL was quantitative for the antigen: NPL 1:5 mass ratio and the formulation was stable for at least six months at 4°C. We assessed the successful delivery of the antigen by NPL in airway epithelial cells and macrophages. These formulations are currently evaluated by the UniVacFlu consortium in mice.One of the main issues of intranasal vaccines is the toxicity that can be elicited by the nose-brain passage of one of their components. We investigated the loading of antigens in NPL and their delivery in airway mucosa. We observed a high endocytosis of NPL and an increased protein delivery into the cells. On a transwell model of the airway mucosa we assessed the absence of transcytosis and paracellular passage of the NPL. In vivo results confirmed the lack of nose-brain passage of the NPL, as NPL were found not to cross the mucosa. Interestingly, we observed an increased nasal residence time of the protein targeted by NPL. The particles after having delivered their payload are totally eliminated through the gastrointestinal tract, making these nanoparticles good candidates for mucosal delivery system. These results highlight the interest of NPL as vectors for mucosal delivery of drugs
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Busch, Marc Gregory. "Evaluation of different SIV plasmid DNA vaccines : a model for HIV vaccine development /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.
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Fredslund, Andersen Rikke. "Developing recombinant poxvirus vaccines." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433236.
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Kohli, Ashish Kumar. "Transcutaneous delivery of vaccines." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415094.
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Russell, Clare. "Immunopotentiation of malaria vaccines." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/12892.
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Plasmids were constructed to encode C3d/PfEMP-1 fusions and expression of recombinant protein in mammalian cells in culture was assayed. Eukaryotic expression of P. falciparum proteins proved to be problematic and a re-condoning approach was adopted to address this. The production of polyclonal anti-PfEMP-1 antibodies in mice was assessed in immunofluorescence assays and in immunoblots with P. falciparum-infected erythrocytes. The data question the suitability of a DNA vaccine approach in the development of a PfEMP-1-based vaccine using C3d. In order to raise specific antibodies to PfEMP-1 and to develop a suitable assay to assess immunogenicity of this antigen, research efforts became focussed on the production of recombinant PfEMP-1 protein, with a view to immunising mice. A recombinant PfEMP-1 domain was expressed in mammalian cells and characterised, demonstrating it to be the ligand involved in binding uninfected erythrocytes. Its reactivity with immune sera and, therefore, its suitability as a malaria vaccine candidate was assessed. Findings highlight the need for further work on the development of methods to produce functionally active recombinant protein. They also show the necessity of improving methods of detecting surface expression of PfEMP-1. The suitability of the Saimiri monkey model for C3d-based vaccination and P. falciparum challenge experiments was assessed. In other species, the receptor for C3d is CR2, expressed on B cells. Saimiri B cells were characterised and their capacity to bind human C3d was demonstrated, indicating that Saimiri is potentially a suitable model for pre-clinical vaccination studies using human C3d-based immunoprotentiation.
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Hartgroves, Lorian Cedar Safir. "Strategies for influenza vaccines." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/5558.
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The high mutation rate of influenza virus results in antigenic drift, meaning that each of the three components in the trivalent influenza vaccine are updated regularly so that the vaccine antigen closely matches the predominant or emerging strain. The production of influenza vaccines from the chosen seed has relied on embryonated chickens eggs for more than 40 years. Recent technological advances have resulted in the evaluation of several cell lines as alternative substrates for influenza vaccine production. Reverse genetics of influenza viruses allows the creation of viruses at will from cDNA. However, licensed cell lines have so far proved unpermissive for virus rescue and permissive lines remain largely unlicensed. A reverse genetics system for the production of influenza vaccines in PER.C6 cells has been developed and optimised. Many recent clinical isolates do not grow in eggs and hence require reassortment with a high growth, egg permissive backbone. Adventitious agents aside, cell lines able to support growth of clinical isolates could be used directly included in the vaccine, without the need for reassortment. However, this could lead to year on year variation in the quality and characteristics of the vaccine. Particularly pertinent, is the variation in the amount of IFN a clinical isolate can induce, which could severely limit yields. Yields and effects of IFN for a panel of high and low inducing viruses are investigated in a number of potential vaccine cell lines. The mechanisms behind virus IFN induction have been investigated. Using a panel of high and low inducing viruses the differences in growth and viral protein expressions, and activation of PRR has been analysed. The IFN response in PER.C6 cells has been characterised. Through an improved understanding of the mechanisms of IFN induction and inhibition, antagonists could be introduced into the vaccine cell line to improve yields.
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Umaimainthan, Palendira. "Improving vaccines against tuberculosis." Thesis, The University of Sydney, 2003. https://hdl.handle.net/2123/27934.
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Tuberculosis (TB) still remains a major health hazard worldwide. The only vaccine currently available, M bovis BCG, has had little impact on the prevalence of TB and there is an urgent need for the development of a new anti-TB vaccine or an improved form of BCG. Subunit vaccines induce effective anti-mycobacterial immune responses and afford partial protection against Mycobacterium tuberculosis infection in animal models. It is necessary however, to increase the efficacy of these vaccines in order to make them potential alternatives to the current BCG vaccine. This study has explored various ways of improving the vaccines against TB in a murine model. DNA vaccines provide a useful model to explore various strategies of increasing vaccine efficacy. Immunity to TB is associated with the development of a strong Th1 T cell response. Therefore to investigate the adjuvant effects of cytokines which could augment Th1 T cell responses, a plasmid secreting both chains of IL-12 from a self-cleaving vector was combined with a DNA vaccine encoding a major secretory protein of M. tuberculosis, antigen 85B (DNA-85). Co-delivery of plasmid IL-12 increased the specific-IFN-Y T cell responses and led to a better protective efficacy of the DNA vaccine. The protection afforded by DNA-85 and plasmid IL-12 was comparable to that of the ECG. This increased protection was also associated with increased specific-IFN-y responses in the draining lymph nodes after challenge. CD40 ligand on T cells stimulates CD40 on dendritic cells (DCs) to increase the immuno-stimulatory potential of DCs and this effect can be induced by agonist anti-CD40 antibodies in vitro. Therefore the adjuvant effects of an agonist anti-CD40 antibody were examined in vivo. Treatment with these antibodies during the immune induction period did not increase the protective effect of ECG or DNA vaccines against M. tuberculosis infection. An alternative approach was to block the down-regulatory effect of cytokine, IL-10 during immune induction period with antibody to the IL-lO receptor. Neutralising the effects of IL-10, however, did not increase the protective efficacy of both DNA and BCG vaccines.
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Hone, David. "Construction of Salmonella vaccines /." Title page, contents and abstract only, 1988. http://web4.library.adelaide.edu.au/theses/09PH/09phh7721.pdf.
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Ishizuka, Andrew Scott. "Pre-clinical and clinical evaluation of the malaria vaccines RH5-VLP and PfSPZ vaccine." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:521c5ef4-7d77-456f-910e-f1f207c80b8d.
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Despite progress through expanded use of bed nets and anti-malarial drugs, Plasmodium falciparum (Pf) malaria caused about 200 million cases and 500,000 deaths in 2015. An ideal vaccine would reduce the burden of disease and interrupt transmission. Despite decades of effort, there is no vaccine that can adequately address the global burden of malaria. This thesis focuses on two potential weaknesses in the parasite life-cycle. First, I investigate two vaccination strategies aimed at improving the antibody response to RH5, an essential and conserved protein for erythrocyte invasion. Due to instability of the resultant recombinant vaccine constructs, these efforts have required re-engineering of the vaccine platform, which remains an ongoing effort. Second, the immunogenicity and mechanism of protection of a live-attenuated whole sporozoite vaccine, PfSPZ Vaccine, was assessed. In a study that examined PfSPZ Vaccine at intravenous (IV) doses between 1.35 &tiles; 105 to 4.5 &tiles; 105 PfSPZ, I demonstrate that PfSPZ antibody responses correlated with durable sterile protection against controlled human malaria infection (CHMI). Surprisingly, the pre-vaccine frequency of Vγ9+Vδ2+ T cells, an innate T cell that recognizes conserved Plasmodium phosphoantigens, also correlated with durable sterile protection. Regarding the mechanism of protection, PfSPZ-specific antibodies as well as CD8 and CD4 T cells in the blood decreased substantially over time, yet sterile protection was maintained. In non-human primates, the CD8 T cell response in the liver at a memory time point was measured to be about 100-fold higher than found in the blood. Collectively, these data suggest that PfSPZ Vaccine confers durable protection in humans by long-lived, tissue-resident CD8 T cells. These findings were extended with a study using 9.0 x 105 PfSPZ, wherein I demonstrate that T cell responses peaked immediately after the first vaccination with minimal T cell activation despite additional immunizations. This suggests that anti-PfSPZ immunity may be limiting the effectiveness of subsequent immunizations. Finally, I examined the T cell response to PfSPZ attenuated by chloroquine (termed PfSPZ-CVac). T cell responses were substantially higher than achieved with comparable PfSPZ Vaccine doses. Additionally, a significantly higher proportion of PfSPZ-specific CD4 T cells were polyfunctional, simultaneously expressing IFN-γ, IL-2, and TNF-α, in subjects that were protected from CHMI. In sum, these studies provide insight into the immunobiology of a protective immune response that may guide future malaria vaccine development efforts.
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McIntyre, Peter. "Measuring the public health impact of vaccines: disease burden, vaccine coverage, safety and effectiveness." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/26251.
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This thesis has eight chapters describing inter-relationships between work in 66 papers published between 1999 and 2020 relevant to the over-arching topic of public health impact of vaccines: measurement of disease burden, vaccine coverage, safety and effectiveness
Chapter 1 outlines the key data sources used: 1. routinely collected administrative data (disease notifications, ICD coded hospitalisations and mortality data) and 2. additional data sources the author had a key role in developing (National Serosurveillance. Paediatric Active Enhanced Surveillance (PAEDS). In chapter 4, development of analysis and reporting of data from the Australian Immunisation Register and in chapter 6 development of platforms for vaccine safety evaluation are described. In Chapter 5, how this work culminated in pilot initiatives to link data sources relevant to public health impact of vaccines in a birth cohort from New South Wales and Western Australia, with the aim of demonstrating the potential for an all-age national capacity, is outlined. Chapter 2 focuses on disease due to Bordetella pertussis and research under the headings of measuring prevalence and severity of pertussis, the effectiveness and impact of pertussis vaccines and clinical trials conducted to evaluate the immunogenicity and safety of acellular pertussis vaccine given within 4 days of birth. Chapter 3 focuses on disease due to Streptococcus pneumoniae and research measuring pneumococcal disease, effectiveness and impact of pneumococcal vaccines and a randomised trial comparing immune responses to pneumococcal conjugate and polysaccharide vaccines in the frail elderly. Chapter 7 includes studies of vaccine impact against Hepatitis B, varicella, meningococcal C disease, mumps and Q fever and Chapter 8 includes four major international reviews of vaccine programs and impact.
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Haile, Melles. "Studies on new tuberculosis vaccine candidates in animal models /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-327-2/.
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Tarcha, Eric J. "Application of Immunoproteomics and Bioinformatics to coccidioidomycosis Vaccinology." University of Toledo Health Science Campus / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=mco1154441973.
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Licata, Matthew J. "The efficacy of combined infectious bronchitis/Newcastle disease vaccines." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 112 p, 2007. http://proquest.umi.com/pqdlink?did=1253510101&Fmt=7&clientId=79356&RQT=309&VName=PQD.
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Parker, Fatima Bibi. "Willingness to participate (WTP) in a future HIV vaccine trial in a high risk sample : perceived barriers and facilitators to participation." Thesis, Link to the online version, 2006. http://hdl.handle.net/10019/1151.
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Lang, Rainer. "Virus-Like particle based vaccines." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-150810.
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Berglund, Peter. "Alphavirus vectors as recombinant vaccines /." Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2657-3.
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Tontini, Marta. "Characterization of carbohydrate based vaccines." Phd thesis, Université de Cergy Pontoise, 2012. http://tel.archives-ouvertes.fr/tel-00825838.
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CHARACTERIZATION OF CARBOHYDRATE BASED VACCINES Variables influencing the immunogenicity and physicochemical properties of glycoconjugate vaccinesMany aspects can influence the immunogenicity of conjugate vaccines and the main variables investigated so far are the size of the saccharide moiety, the saccharide:protein ratio in the purified conjugate, the conjugation strategy, the nature of the spacer and the protein carrier. The size of the saccharide moiety and saccharide/protein ratio were investigated in different works such as Seppälä and Mäkelä in one of the first studies on the effect of size and chemistry on the immunogenicity of dextrans-protein conjugates found that dextrans of low molecular weight conjugated to chicken serum albumin, induced strong anti-dextran responses in mice, while increasing the dextrans' size resulted in reduced immunogenicity.47 Peeters et al. showed that a synthetic tetramer of Hib capsular polysaccharide repeating unit, conjugated to a protein carrier, induced in adult mice and non-human primates antibody levels comparable to a commercial Hib conjugate and higher than those induced by a trimer, indicating that for Hib a minimum of eight sugars is needed for a proper immunological response.48 Laferriere et al. found little influence of the carbohydrate chain length on the immunogenicity of pneumococcal conjugate vaccines in mice.49 Pozsgay et al. studied the immunogenicity in mice of synthetic Shigella dysenteriae type 1 LPS oligosaccharides conjugated to human serum albumin (HSA). The authors found that octa-, dodeca-, and hexadecasaccharide fragments induced high levels of lipopolysaccharide binding IgG antibodies in mice after three injections and were superior to a tetrasaccharide conjugate. The influence of the carbohydrate/protein ratio was different for the three conjugates. The octasaccharide-HSA conjugate with the highest density evoked a good immune response, while in the case of dodeca- and hexadecasaccharide conjugates, the median density was optimal.50 These studies suggest that oligosaccharide chain length and hapten loading might be interconnected in determining the immunogenicity of glycoconjugate vaccines. The spacer is a short linear molecule that is generally linked to the polysaccharide chain or to the protein or to both moieties, depending on the chemistry, used to facilitate the coupling between the protein and sugar. There are evidences in the literature which suggest that rigid, constrained spacers like cyclohexyl maleimide, elicit a significant amount of undesirable antibodies, with the risk of driving the immune response away from the targeted epitope on the hapten.51 52 The use of a flexible alkyl type maleimido spacer has been reported as a way to overcome the previous observed immunogenicity of cyclic maleimide linkers.53 A number of protein carriers have been used so far in preclinical and clinical evaluation of conjugate vaccines. 54 55 56 57 58 59 60Proteins such as diphtheria and tetanus toxoids, which derive from the respective toxins after chemical detoxification with formaldehyde, were initially selected as carrier because of the safety track record accumulated with tetanus and diphtheria vaccination. CRM197, a non-toxic mutant of diphtheria toxin61 which instead does not need chemical detoxification, has been extensively used as carrier for licensed Hib, pneumococcal, meningococcal conjugate vaccines and for other vaccines being developed. An outer membrane protein complex of serogroup B meningococcus has been used by Merck as carrier for their Hib conjugate vaccine.62 GSK in their multivalent pneumococcal conjugate vaccine introduced the use of the Hib-related protein D as carrier for most of the polysaccharides included into the vaccine.63 64 The team of John Robbins made extensive use of the recombinant non toxic form of Pseudomonas aeruginosa exo-toxin as carrier for Staphylococcus aureus type 5 and 8 as well as for Salmonella
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Sheu, Eric G. "Immunology of T cell vaccines." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288552.
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Jenner, Dominic Charles. "Sub-Unit Vaccines for Brucella." Thesis, Open University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504266.
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Xu, Damo. "Experimental vaccines against #Leishmania major'." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362657.
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Chen, Caleb Gonshen. "DNA-based vaccines against cancer." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405968.
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Longley, Rhea Jessica. "Liver-stage vaccines for malaria." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:b5c9821c-db32-4b66-a315-02541e62f566.
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The development of an efficacious P. falciparum malaria vaccine remains a top priority. Pre-erythrocytic vaccine efforts have traditionally focussed on two well- known antigens, CSP and TRAP, yet thousands of antigens are expressed throughout the liver-stage. The work described in this thesis aimed to assess the ability of other pre-erythrocytic antigens to induce an immune response and provide protective efficacy against transgenic parasites in a mouse model. Research undertaken in our laboratory has demonstrated the ability of prime-boost viral vectored sub-unit vaccination regimens to elicit high levels of antigen-specific T cells. Eight candidate antigens were therefore expressed individually in the viral vectors ChAd63 and MVA. Two antigens, PfLSA1 and PfLSAP2, were identified that confer greater protective efficacy in inbred mice than either CSP or TRAP. PfLSA1 was also able to induce almost complete sterile efficacy in outbred mice, suggesting this vaccine should be assessed in a clinical trial. Immune responses to the candidate antigens were also assessed in human volunteers following their first exposure to controlled malaria infection. The antigen TRAP was further characterised by epitope mapping in volunteers vaccinated with ChAd63-MVA ME-TRAP. However, no functional T cell assay exists to measure inhibition of P. falciparum liver-stage parasites. An improved murine in vitro T cell killing assay was developed, and preliminary experiments were conducted that demonstrate the potential and promise of a P. falciparum T cell killing assay. Such assays will not only allow mechanistic studies to be undertaken, but could also change the way we screen pre-clinical liver-stage vaccines.
35
Kayaga, Justina. "Allogenic tumour vaccines for melanoma." Thesis, St George's, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394404.
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Li, Yihang Kaltenboeck Bernhard. "Therapeutic vaccines against chlamydial diseases." Auburn, Ala., 2008. http://hdl.handle.net/10415/1417.
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Palladini, Arianna <1978>. "Preclinical development of cancer vaccines." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/2035/1/Palladini_Arianna_tesi.pdf.
Full textAbstract:
Triplex cell vaccine is a cancer immunopreventive cell vaccine that can prevent almost completely mammary tumor onset in HER-2/neu transgenic mice. A future translation of cancer immunoprevention from preclinical to clinical studies should take into account several aspects. The work reported in this thesis deals with the study of three of these aspects: vaccine schedule, activity in a therapeutic set-up and second-generation DNA vaccines. An important element in determining human acceptance and compliance of a
treatment protocol is the number of vaccinations. In order to improve the vaccination schedule a minimal protocol was searched, i.e. a schedule consisting of a lower number of administrations than standard protocol but with a similar efficacy. A candidate optimal protocol was identified by the use of an in silico model, SimTriplex simulator. The in vivo test of this schedule in HER-2/neu transgenic mice only partially confirmed in silico predictions. This result shows that in silico models have the potential ability to aid in searching of optimal treatment protocols, provided that they will be further tuned on experimental data. As a further result this preclinical study highlighted that kinetic of antibody response plays a major role in determining cancer prevention, leading to the hypothesis of a threshold that must be reached rapidly and maintained lifetime. Early clinical trials would be performed in a therapeutic, rather than preventive, setting. Thus, the activity of Triplex vaccine was investigated against experimental lung metastases in HER-2/neu transgenic mice in order to evaluate if the immunopreventive Triplex vaccine could be effective also against a pre-existing tumor mass. This preclinical model of aggressive metastatic development showed that the vaccine was an efficient treatment also 4 for the cure of micrometastases. However the immune mechanisms activated against tumor mass were not antibody dependent, i.e. different from those preventing the onset of primary mammary carcinoma. DNA vaccines could be more easily used than cellular ones. A second generation of Triplex vaccine based on DNA plasmids was evaluated in an
aggressive preclinical model (BALBp53neu female mice) and compared with the preventive ability of cellular Triplex vaccine. It was observed that Triplex DNA vaccine was as effective as Triplex cell vaccine, exploiting a more restricted immune stimulation.
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Palladini, Arianna <1978>. "Preclinical development of cancer vaccines." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/2035/.
Full textAbstract:
Triplex cell vaccine is a cancer immunopreventive cell vaccine that can prevent almost completely mammary tumor onset in HER-2/neu transgenic mice. A future translation of cancer immunoprevention from preclinical to clinical studies should take into account several aspects. The work reported in this thesis deals with the study of three of these aspects: vaccine schedule, activity in a therapeutic set-up and second-generation DNA vaccines. An important element in determining human acceptance and compliance of a
treatment protocol is the number of vaccinations. In order to improve the vaccination schedule a minimal protocol was searched, i.e. a schedule consisting of a lower number of administrations than standard protocol but with a similar efficacy. A candidate optimal protocol was identified by the use of an in silico model, SimTriplex simulator. The in vivo test of this schedule in HER-2/neu transgenic mice only partially confirmed in silico predictions. This result shows that in silico models have the potential ability to aid in searching of optimal treatment protocols, provided that they will be further tuned on experimental data. As a further result this preclinical study highlighted that kinetic of antibody response plays a major role in determining cancer prevention, leading to the hypothesis of a threshold that must be reached rapidly and maintained lifetime. Early clinical trials would be performed in a therapeutic, rather than preventive, setting. Thus, the activity of Triplex vaccine was investigated against experimental lung metastases in HER-2/neu transgenic mice in order to evaluate if the immunopreventive Triplex vaccine could be effective also against a pre-existing tumor mass. This preclinical model of aggressive metastatic development showed that the vaccine was an efficient treatment also 4 for the cure of micrometastases. However the immune mechanisms activated against tumor mass were not antibody dependent, i.e. different from those preventing the onset of primary mammary carcinoma. DNA vaccines could be more easily used than cellular ones. A second generation of Triplex vaccine based on DNA plasmids was evaluated in an
aggressive preclinical model (BALBp53neu female mice) and compared with the preventive ability of cellular Triplex vaccine. It was observed that Triplex DNA vaccine was as effective as Triplex cell vaccine, exploiting a more restricted immune stimulation.
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Li, Tsz-wai, and 李梓維. "Efficacy of combined influenza and 23-valent pneumococcal polysaccharide vaccines in chronic smokers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/202310.
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Background
Chronic smokers are at risk of premature death associated with underlying pulmonary or cardiovascular diseases. Dual influenza and pneumococcal vaccination has been shown to prevent death and hospitalization secondary to pulmonary or cardiovascular diseases in elderly persons. Its effect in chronic smokers remained unknown.
Methods
This is a prospective randomized open-labeled trial conducted from April 2010 to March 2013, comprising adult patients aged less than 50 years who were chronic smokers. Subjects were randomly assigned into 4 groups. Group 1 (study group) patients received both trivalent influenza vaccine (TIV) and the 23-valent polysaccharide pneumococcal vaccine (PPV). There were 3 control groups: Group 2 patients received the TIV only. Group 3 patients received the PPV only and Group 4 patients did not receive any vaccines. The TIV used was the Vaxigrip® (Sanofi Pasteur, France) and the PPV used was the Pneumovax®23 (Merck, USA). All enrolled patients were follow-up for 24 months post vaccination. Patient details, Charlson comorbidity index, medications, subsequent hospitalization, diagnosis and mortality were recorded and analyzed.
Results
A total of 1006 subjects were enrolled and completed the study (Group PPV+TIV: 250; Group TIV: 254, Group PPV: 250 and Group None: 259). The baseline demographics and Charlson comorbidity index were similar among subjects in the 4 groups. The median age was 48 years and 85.9% were male patients. Significantly fewer subjects who received the dual vaccination (Group PPV+TIV) were hospitalized (p<0.001), with shorter mean length of stay (p<0.001), and less frequent hospitalization (p<0.001) for cardiovascular or respiratory diseases than no vaccination (Group None) or single vaccination (Group TIV and Group PPV). Multivariate analysis demonstrated that dual vaccination with PPV + TIV was the only independent factor associated with reduced risk of hospitalization (p<0.001; relative risk 0.288; 95% CI 0.101-0.154). There was no difference in mortality rate among the groups. Both vaccinations were well tolerated and no serious adverse events were reported.
Conclusion
Dual influenza and pneumococcal vaccinations prevented chronic smokers against hospitalization secondary to pulmonary or cardiovascular causes. Annual influenza and a single pneumococcal vaccination should be promoted among chronic smokers.published_or_final_version
Microbiology
Master
Master of Medical Sciences
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Zhou, Jingying, and 周京颖. "Efficacy and mechanism of PD1-based DNA vaccines in enhancing HIV-1 Gag-specific immunity." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50662338.
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Human immunodeficiency virus type 1 (HIV-1) has caused more than 70 million infections worldwide since its discovery, with half of the infected already died by the end of 2011 as a result of HIV-progression to acquired immunodeficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) is capable to extend the lifespan of HIV patients but economic burden and emergence of resistant HIV strains pose immediate problems in the care of HIV patients. Furthermore, HAART cannot clear virus. Therefore, tremendous efforts have tried to develop an effective HIV vaccine in the last thirty years but only partial efficacy (31%) was achieved in the recent Thai RV144 clinical trial. Hence, new vaccine and understanding the mechanism are required now and in the future.
In this study, two novel DNA vaccine strategies that utilized programmed death-1 (PD-1) or its isoform to improve immunogenicity of DNA vaccine for HIV-1 Gag p24 by acting on dendritic cells are described. The molecule PD-1 delivers negative regulatory signals to T cells through interacting with its ligands PD-L1 and PD-L2, while blocking this signal could functionally rescue the “exhausted” T cells during chronic infection such as HIV-1. The first DNA vaccine involves the fusion between HIV-1 Gag p24 antigen and soluble PD1 for effective targeting to DCs while improving antigen uptake and DC maturation, which in turn elicited consistently high frequencies of HIV-1 Gag-specific, broadly reactive, polyfunctional, long-lived and cytotoxic CD8+ T cells, in addition to robust anti-Gag antibody titers in mouse. The mechanism behind the action of this vaccine (sPD1-p24fc) is based on engagement of cross-presentation to CD8+ T cells, and induction of Th1 cytokines.
The second DNA vaccine utilized a novel isoform of human PD1 (Δ42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain discovered in healthy PBMC donors. Interestingly, Δ42PD1 does not engage PD-L1/PD-L2 but its recombinant form could induce pro-inflammatory cytokines. When Δ42PD1 was used as an intramolecular adjuvant to develop a fusion DNA vaccine with HIV-1 Gag p24 antigen (sΔ42PD1-p24fc), enhanced DC uptake was also observed. When mice was vaccinated with this vaccine, significantly enhanced anti-p24 IgG1/IgG2a antibody, p24-specific T cells responses with functionally improved proliferative and cytolytic capacities were also identified. Importantly, both of these vaccines enhanced antigen-specific immunity and provided protection against pathogenic viral challenge as well as tumor growth in mice.
Overall, the induction of high frequency of durable and protective Gag-specific T cell immunity, especially CD8+ T cell immunity using these two vaccines have important implications for vaccine development and immunotherapy against HIV-1 and other pathogens.published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
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Yang, Zheng, and 楊爭. "Identification of non-HIV-derived (poly)peptides as primary immunogens for HIV-1 vaccine development and localization of two dominant ADCC epitopes on hemagglutinin antigen of pandemic H1N1 influenza virus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208007.
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Development of effective vaccines against mutable viruses (i.e HIV-1 and influenza) remains a big challenge. Antibody-dependent cell-mediated cytotoxicity (ADCC) has been found to be a key component of immune protection against viral infections in vivo. Therefore, vaccine immunogens that elicit broadly neutralizing antibodies with high ADCC are desired for vaccine development. This study is to identify primary immunogens that can initiate somatic maturation of germline antibodies of known broadly neutralizing HIV-1 antibodies (bnAbs) for HIV vaccine development and to localize dominant ADCC epitopes on hemagglutinin (HA) of pandemic H1N1 influenza virus for development of a flu vaccine.
Based on the observations that known HIV-1 bnAbs have extensive somatic mutation compared to their germline versions and that HIV-1 envelope (Env) glycoprotein lacks measurable binding to putative germline antibodies of known bnAbs, we hypothesized that non-HIV-derived (poly)peptides may serve as primary immunogens to trigger somatic maturation of germline antibodies of bnAbs, leading to elicitation of intermediate antibodies (iAbs) that can further mature to HIV-1 bnAbs upon Env vaccination or HIV-1 infection. Using b12 as a model bnAb, we identified five non-HIV-derived (poly)peptides that bound to putative b12 germline and iAbs, and immunized rabbits with the (poly)peptide priming followed by Env boosting. Rabbit immunization with (poly)peptides alone induced high titers of antibodies that were cross-reactive with gp140SF162 trimer and resurfaced Env RSC3, and the serum IgGs neutralized SF162 and JRFL. These results suggest that the (poly)peptides might structurally mimic CD4bs of Env. Priming rabbits with (poly)peptides followed by boosts with gp140SF162 and RSC3 resulted in antibodies capable of competing with b12 for binding to gp140SF162 trimer and neutralizing cross-clade isolates, while control rabbits without priming produced antibodies that were unable to compete with b12 for gp140SF162 trimer binding, and the serum IgGs neutralized only 3 clade B isolates. Our results provide proof of concept that non-HIV-derived (poly)peptides may serve as primary vaccine immunogens to initiate guided immune responses towards bnAbs.
HA protein has high level of immunogenicity and considered the most important target for immune protection against influenza virus infection. Several potent HA-specific bnAbs have been reported with their conserved neutralizing epitopes revealed, but there has been no report so far about ADCC epitopes on HA. Using yeast display and flow cytometry assisted cell sorting, we mapped the epitope of convalescent plasma IgGs with different ADCC activity, we identified two dominant ADCC epitopes, designated HA-E1 [AA92-117] and HA-E2 (AA 124-159), on HA of 2009 pandemic H1N1 influenza virus. E1 and E2 overlapped with the immunodominant epitopes of HA. Depletion of purified patient plasma IgGs with yeast cells expressing E1 or E2 peptides decreased ADCC activity of the IgGs. E1 and E2 sequences are highly conserved in H1N1 strains, but less so in other subtypes of influenza A viruses. Our study may aid in designing immunogens that can elicit antibodies with high ADCC activity. Vaccine immunogens designed to include the structural determinants of potent bnAbs and ADCC epitopes may confer a comprehensive immune protection against influenza virus infection.published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
42
Cassan, Simone de. "Toward improved blood-stage malaria vaccines : characterising the underlying immunogenicity of vaccine adjuvants and vectors." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.560918.
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The vaccine field generally accepts that the induction of high-titre antibodies will be necessary to prevent the invasion of erythrocytes utilising vaccines targeting the blood-stage of malaria. Protein-in-adjuvant formulations are commonly used to achieve such responses. However, their clinical development can be limited by the reactogenicity of some of the most potent pre-clinical adjuvants and the cost and complexity of licensing new adjuvants for human use. Work in this thesis describes the comparative assessment of classical adjuvants such as alum to new pre-clinical adjuvants and adjuvants in clinical development for the induction of high and sustained antibody and T cells responses. These adjuvants induced a broad range of antibody responses when used in a three-shot protein-in-adjuvant regime using the model antigen ovalbumin and leading blood-stage malaria vaccine candidate antigens. Surprisingly, this range of antibody immunogenicity was greatly reduced and antibody responses were of a comparably high magnitude when a protein-in-adjuvant vaccine was used to boost antibody responses primed by an AdHuS vaccine recombinant for the same antigen. This adenovirus prime, protein boost regime also induced a more cytophilic antibody response and demonstrated improved efficacy of merozoite surface protein-l protein vaccines against a high-dose Plasmodium yoe/ii blood-stage challenge. Investigating the underlying differences between the vaccine platforms used suggests the improved boosting observed following an adenovirus prime is not due to differences in antigenic dose exposed to the immune system or extended immunisation intervals between adenovirus and protein vaccines, but rather appears to be inherent to the adenoviral vector, which induces more germinal centre cells and Tfollicular helper cells. Attempts to further enhance the immunogenicity of viral vectors through the direct addition of the adjuvants chloroquine and Adju-Phos" was not successful. 1.
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De, Cassan Simone. "Towards improved blood-stage malaria vaccines : characterising the underlying immunogenicity of vaccine adjuvants and vectors." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711629.
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BOEHNER, CONSTANCE WILLIAMS. "FACTORS AFFECTING STD VACCINE ACCEPTANCE IN COLLEGE STUDENTS." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1014411621.
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Marsay, Leanne. "Evaluation of immune correlates to TB vaccines." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572645.
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Development of an improved TB vaccine is hindered by the lack of a correlate of ,~.-r protection. Efficacy of TB vaccines in humans can only be a"S~essed by expensive and time consuming trials within TB endemic areas, which are limited; therefore, it is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. Work in this thesis describes the development and evaluation of different MGIAs for their ability to detect TB vaccine induced mycobacterial growth inhibition. The mycobacterial growth indicator tube (MGIT) MGIA reproducibly demonstrated mycobacterial growth inhibition in splenocytes from BCG vaccinated compared with naive mice, which corresponded with in vivo protection from M. tb challenge. This assay also discriminated between PBMC from naive and BCG/BCG-MVA85A vaccinated macaques. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between naive and BCG vaccinated mice. T H 1 responses including IFN-y with NOS2 expression were enhanced in BCG vaccinated mice, indicating a possible mechanism for mycobacterial growth inhibition in BCG vaccinated mice. Further investigation into whether the MGIT assay can be used as a correlate of protection from M. tb in humans and animals is warranted.
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Islam, Amina Mahmood. "A qualitative study of women's attitudes towards the introduction of the HPV vaccination in Singapore." Thesis, Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41710034.
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Okay, Sezer. "Development Of Recombinant Vaccines Composed Of Plpe And Omph From Pasteurella Multocida A:3." Phd thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613980/index.pdf.
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Pasteurella multocida serotype A:3 is a gram-negative bacterial pathogen which is one of the causative agents of shipping fever in cattle. In this study, ompH and two fragments of plpE gene (plpEN and plpEC) were cloned from the genomic DNA of P. multocida P-1062 (ATCC 15743, serotype A:3) and plpEN-ompH and plpEC-ompH fusions were constructed. In vitro expression of the genes was shown in HEK-293 cells. Later, full-length plpE gene was cloned and the recombinant proteins were expressed in E. coli and purified. Three DNA vaccine formulations, namely pCMV-ompH, pCMV-plpEN-ompH and pCMV-plpEC-ompH and five recombinant protein based vaccines, PlpEN-OmpH, PlpEC-OmpH, OmpH, PlpEC and PlpE were generated. Recombinant proteins were formulated with at least one of the adjuvants: alum, CpG, alum-CpG, oil based and oil based-CpG. BALB/c mice were immunized with these vaccine formulations and their sera were used for the evaluation of antibody and serum IFN-&gammatiters. Protective capacities of the vaccines were also evaluated via challenge of mice with 10 LD50 of P. multocida A:3. DNA vaccines induced immune responses, but did not provide protection. All protein vaccine formulations increased antibody levels and CpG containing formulations enhanced serum IFN-&gamma
titers. 100 µ
g of PlpEC-OmpH protein adsorbed on alum adjuvant conferred 40% protection while no protection was obtained with PlpEN-OmpH. Next, the effects of CpG, or its alum and oil based combinations as adjuvants were investigated on PlpEC-OmpH mediated protection. The vaccine formulation composed of PlpEC-OmpH and oil based-CpG adjuvant conferred 100% protection. Finally, the mice were vaccinated with recombinant OmpH, PlpEC and PlpE formulated with oil based-CpG adjuvant. OmpH, PlpEC and PlpE formulations provided 50%, 60% and 100% protection, respectively. These findings implicated that recombinant PlpE and PlpEC-OmpH fusion proteins when formulated with oil based-CpG adjuvant are potent acellular vaccine formulation candidates against shipping fever.
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Boros, Christina Ann. "Factors affecting the immunogenicity and protective efficacy of routine childhood immunisations." Title page, contents and abstract only, 2001. http://web4.library.adelaide.edu.au/theses/09PH/09phb736.pdf.
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Includes list of publications arising from the thesis. Bibliography: leaves 327-341. Examines the effect of adverse storage on the immunogenicity of pertussis, diphtheria and tetanus vaccines, the protective efficacy of pertussis vaccines and the effect of premature birth on antibody response to routine childhood immunisations.
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Wurzenberger, Cornelia. "Dendritic cell vaccines in tumor immunotherapy." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-95530.
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Brown, Nathan Edward Charles. "Vaccines for Infection Salmon Anemia Virus." Fogler Library, University of Maine, 2003. http://www.library.umaine.edu/theses/pdf/BrownNEC2003.pdf.
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