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Dissertations / Theses on the topic 'Oral vaccines'
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1
New, James Stewart. "Plant-made oral vaccines evaluation of capsules." Honors in the Major Thesis, University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/493.
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Antigen expression through the Chloroplast Transformation Technology (CTT) produces bioencapsulated subunit-vaccines, capable of eliciting immune responses when delivered orally. Considerable challenges to effective plant-based vaccines are the normalization of dosage and preservation of accumulated antigen, which is complicated by variable high water content and protease activity. This study critically examines the efficacy of lyophilization in dehydrating plant-tissues and preserving plant-derived antigens with vaccine potential. Lyophilization was optimized through gravimetric analysis using lettuce expressing Protective Antigen (PA) of Bacillus anthracis (LS-HPAG) and the human autoantigen Proinsulin (Pins) fused to Cholera toxin subunit B (LS-CTB-Pins). Lyophilization for 48-hours was sufficient treatment to reduce lettuce to 4.57% of its original weight, which retained .058% water content in the bound state; these levels corresponded with oven-dried controls while antigen was stabilized for over a year of storage at room temperature. A simulated gastric fluid assay was applied to evaluate stability of plant derived antigens during digestion. It was observed that lettuce plant cells conferred protection through antigen bioencapsulation for up to an hour under enzymatic digestive conditions. LS-HPAG immunogenicity was then demonstrated through the induction of a PA-specific IgG response by through oral boosting of C57/BL6 test mice. Survival during toxin challenge demonstrated a protective immune response if 40% of animal immunized by plant-derived PA. Lastly, the inclusion of excipient and adjuvant additives will be considered and utilized for the development of prototype vaccine capsule formulations.B.S.
Bachelors
Medicine
Molecular Biology and Microbiology
2
Morgan, Suzanne M. "Development of oral vaccines : evaluation of polymer-peptide conjugates." Thesis, Keele University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333420.
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Bauer, Heike. "Towards a second generation of Salmonella-mediated oral DNA vaccines." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972155368.
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Ashby, Deborah. "Feasibility of testing recombinant oral attenuated Salmonella vaccines in rabbits." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6248.
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An effective vaccine against chancroid could take the place of therapeutic control programs, offering long-lasting protection without the risk of widespread drug resistance. Orally administered recombinant attenuated Salmonella strains are used as vaccine vectors to deliver heterologous, pathogen-derived antigens to intestinal mucosal associated lymphoid tissue, and to provide vaccine adjuvancy. Chancroid vaccines are tested in a temperature-dependent rabbit model of experimental H. ducreyi infection. However, testing of recombinant attenuated Salmonella strains as vaccine vectors has never been done in rabbits; it is usually done in mice. Anatomic and physiologic differences may limit this approach to the demonstration of vaccine feasibility in rabbits. A three-part study was designed to assess the feasibility of testing attenuated Salmonella vector vaccines in rabbits. The questions asked were, (1) what is the maximum tolerated oral dose and minimum immunogenic oral dose of attenuated Salmonella in rabbits, (2) can a recombinant antigen expressed in the attenuated vector be recognized by the rabbit immune system, and (3) will experimental H. ducreyi infection in rabbits after oral Salmonella vaccination function as a comparative quantitative virulence assay to permit vaccine evaluation? (Abstract shortened by UMI.)
5
Tyrer, Peter Charles, and n/a. "Targeting M-cells for oral vaccine delivery." University of Canberra. Health Sciences, 2004. http://erl.canberra.edu.au./public/adt-AUC20060427.122012.
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An in vitro model of the follicle-associated epithelia that overlie the Peyer's patches of the
small intestine was developed and validated to examine the mechanisms of mucosal antigen
sampling. This model displays many phenotypic and physiological characteristics of M cells
including apical expression of [alpha]5[beta]l integrin and enhanced energy dependent participate
transport. CD4+ T-cells were shown to be an important influence on the development of Mlike
cells.
The model was used to examine the M cell mediated uptake of several putative whole-cell
killed bacterial vaccines. Greater numbers of non-typeable Haemophilus influenzae NTHi
289, NTHi 2019, Escherichia coli 075 HMN and Streptococcus pneumoniae were
transported by model M cells compared to control Caco-2 enterocyte-like cells. Studies in
isolated murine intestine segments confirmed the selective uptake of NTHi 289 and
Escherichia coli demonstrating that intestinal mucosal sampling of these antigens is
performed by M cells. Pseudomonas aeruginosa was not absorbed as whole cell bacteria but
as soluble antigen, as indicated by the presence of bacterial DNA in the cytoplasm of
epithelial cells. These results suggest that bacteria such as NTHi and E. coli are sampled by
the mucosal immune system in a different manner to that of bacteria such as Pseudomonas.
A number of potential cell surface receptors were investigated to identify which molecules
are responsible for intestinal uptake whole-cell killed bacteria. Immunofluorescence studies
detected the presence of toll-like receptor-2, toll-like receptor-4, PAF-R and [alpha]5[beta]l integrin
on in vitro M-like cell cultures. Examinations of murine intestine confirmed the presence of
TLR-4 and PAF-R. TLR-4 was found in small quantities and on M cells. In contrast to the M
cell model, TLR-2 expression in the murine intestine was sparse.
Receptor inhibition experiments provided evidence for the involvement of TLR-4, PAF-R
and [alpha]5[beta]l integrin in M cell uptake of killed bacteria both in vitro and in vivo.
This thesis has contributed valuable information regarding the mechanisms of uptake of
whole-cell killed bacteria by the intestinal mucosal immune system. For the first time, M cell
sampling of whole-cell killed bacteria has been demonstrated. Furthermore, the receptors
involved in these processes have been identified. This information will be of great use in the
development and optimisation of new oral vaccines.
6
Mahbubani, Krishnaa Trishna Ashok. "Vehicles for the oral delivery of live bacteria." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608290.
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Maloy, Kevin Joseph. "The basis of the oral and parenteral adjuvant properties of immune stimulating complexes (ISCOMS)." Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321045.
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Krüger, Carina. "Passive immunization against oral pathogens /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-960-9/.
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Darton, Thomas C. "Application of a challenge model to assess the protective efficacy of oral typhoid vaccines in humans." Thesis, University of Oxford, 2014. https://ora.ox.ac.uk/objects/uuid:4f0dfdf5-d2b0-402d-8910-e17c72eb832c.
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Human infection by Salmonella Typhi has been occurring for the last 50,000 years and still accounts for ∼ 22million new cases each year worldwide. Through faeco-oral transmission, this human-restricted infection disproportionately affects the most impoverished sections of endemic communities where adequate sanitation infrastructure and effective vaccination approaches are lacking. Development of new control measures to accurately measure the burden of disease and to prevent infection with new vaccine candidates are hindered by an incomplete understanding of host-pathogen interactions and of what constitutes a protective human response after exposure. In this thesis I describe the practical application of a recently developed human challenge model of typhoid infection in assessing new control measures, including the evaluation of the oral single-dose vaccine candidate, M01ZH09. In performing a large, double-blind, placebo-controlled study, I was able to measure the direct protective efficacy (PE) of vaccination with either M01ZH09 or 3-dose Ty21a by performing human challenge with 104CFU Salmonella Typhi, Quailes strain, 28-days later. Using clinical and microbiological definitions to confirm typhoid diagnosis during a 14-day period after ingestion, I found insignificant levels of protection afforded by a single dose of M01ZH09 (12.9%), and a low PE after Ty21a vaccination (35%), demonstrating the stringency of the model and the endpoints used. Many additional insights into pathogen dynamics and host responses were found highlighting several important characteristics of oral vaccination. M01ZH09 was highly immunogenic, and both active vaccines significantly reduced bacterial burden (bacteraemia and stool shedding) while having no effect on symptomatic severity of infection in those diagnosed. M01ZH09 receipt resulted in a significantly longer incubation period, suggesting underlying protective responses were being generated. Further findings included the first objective demonstration of primary bacteraemia occurring after typhoid exposure, and frequent asymptomatic infection or stool shedding in those exposed but remaining well. Overall, these data also demonstrated significant protective effects against challenge by anti-Vi antibody status and age at baseline. Taking these factors into account, M01ZH09 and Ty21a vaccination did convey an overall protective advantage against developing typhoid infection, each reducing the risk of diagnosis by ~two-fold during the challenge period.
10
Zheng, Songyue, and 郑嵩岳. "Comparative immunological evaluation of recombinant Salmonella typhimurium strains expressing model antigens as live oral vaccines." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49617734.
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Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines.
Here, a series of recombinant Salmonella Typhimurium strains were constructed to express either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. To investigate different delivery and expression methods, antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in the cytoplasm, or the outer membrane. In addition, combinations of two expression strategies were employed to evaluate the efficacy of combined delivery approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities, the immunogenicity of the constructed recombinant Salmonella strains was evaluated and compared in mice. Using soluble model antigen EGFP, my results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, while eukaryotic expression or colonization with good construct stability is critical for T cell responses. For insoluble antigen model HA, the outer membrane strategy induced better B cell and T cell responses than cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited as initially expected.
Based on the advantages, deleterious or synergistic effects of different strategies identified in this study, I conclude that different construction strategies of recombinant Salmonella vaccine strains are needed for different forms of antigens (soluble or insoluble antigens). If the antigen (such as EGFP) is soluble and easily expressed in Salmonella, a low-copy plasmid-based strategy should be employed, as it can provoke both strong B cell and T cell responses with better plasmid stability. If a T cell response is preferred, a eukaryotic plasmid, or chromosome-based, cytoplasmic-expression strategy may achieve better results. For heterologous antigens that are likely to be expressed in an insoluble form inside Salmonella (such as HA), an outer membrane-targeting approach is recommended. In addition, I found that the combination of two expression strategies did not enhance the immune response, and hence I caution the use of such an approach.published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy
11
Cheng, Woei Ping. "New amphiphilic polyethylenimines (PEIs) for oral delivery of poorly soluble drugs and DNA vaccines." Thesis, University of Strathclyde, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415368.
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Magalo, Simone Issaca. "Evaluation of immunity and protection induced in pullets by the V4 oral vaccine against a pneumotropic velogenic Newcastle disease virus (NDV) strain." Diss., University of Pretoria, 2002. http://upetd.up.ac.za/thesis/available/etd-11042005-140706/.
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Scaramuzzi, Karina. "Efeito adjuvante da sílica mesoporosa nanoestruturada SBA-15 na imunização pela via oral." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-07102009-091507/.
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A sílica nanoestruturada SBA-15 é um polímero que devido à suas propriedades físico-químicas apresenta grande potencial como adjuvante de mucosas. A imunização pela via oral de camundongos com a vacina contra Hepatite A ou gama globulina humana adsorvida a SBA-15 revelou aumento nos títulos de anticorpos específicos IgG e IgA, comprovando que a sílica não interfere na polarização da resposta imunológica dos tipos TH1 ou TH2. Ensaios por citometria de fluxo indicaram que a SBA-15 atuou no recrutamento de fagócitos e no aumento dos números de linfócitos B e T nas placas de Peyer e linfonodos mesentéricos de animais imunizados, sugerindo a proliferação de células imunocompetentes. A administração subcutânea de SBA-15 em camundongos geneticamente selecionados para máxima [AIRMAX] ou mínima [AIRMIN] resposta inflamatória aguda confirmou o baixo potencial inflamatório e a não toxicidade dessa nanopartícula. Os resultados comprovam que a SBA-15 é um adjuvante seguro e eficiente, especialmente nas imunizações pela via oral.The nanostructured SBA-15 silica is a polymer that due to its physicochemical properties shows great potential as a mucosal adjuvant. Immunization by the oral route of mice with Hepatitis A vaccine or human gama globulin adsorbed/encapsulated in SBA-15 revealed increases in the IgG e IgA specific antibody titers and showed that this silica does not interfere in the polarization of TH1 or TH2 immune responses. Flow cytometry assays demonstrated that SBA-15 was efficient in the recruitment of phagocytes and in the increasing numbers of B and T lymphocytes in Peyer´s patches and mesenteric lymph nodes of immunized mice, promoting the proliferation of immunocompetent cells. Subcutaneous administration of SBA-15 in the genetically selected mice for high [AIRMAX] or low [AIRMIN] acute inflammatory responses indicated the low inflammatory potential and the non-toxicity of this nanoparticle. Results ascertain that SBA-15 silica is an effective and safe adjuvant especially in immunizations by the oral route.
14
Parker, Edward. "Influence of the intestinal microbiota on the immune response to oral poliovirus and rotavirus vaccines in a low-income community in south India." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/42504.
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Oral vaccines have consistently underperformed in the low-income countries where they are needed most. This has formed a potent obstacle to several public health initiatives that rely on such vaccines, including the polio eradication endgame. This thesis examines the hypothesis that the composition of the intestinal microbiota – including both pathogenic and commensal microbes – contributes to the impaired performance of oral vaccines in low-income countries. Based on a systematic review and meta-analysis, we observed a decrease in the likelihood of responding to oral poliovirus vaccine (OPV) among infants with concurrent enterovirus infections or diarrhoea. We subsequently tested for multiple bacterial, viral, and eukaryotic enteropathogens and sequenced the 16S rRNA gene (to characterise the total bacterial microbiota) among infants living in a semi-urban slum in south India who had received Rotarix (an oral rotavirus vaccine) and OPV at 6 and 10 weeks of age. We did not observe significant differences in bacterial microbiota composition according to seroconversion status for either vaccine. However, the presence of bacterial pathogens was positively correlated with Rotarix response and negatively correlated with OPV response, suggesting that distinct mechanisms may impact these vaccines. The same methods were applied to samples from 6–11 month-old infants who had received OPV after a 3-day course of azithromycin or placebo. Once again, the association between bacterial microbiota composition and vaccine outcome was modest, although microbiota diversity was negatively correlated with vaccine poliovirus replication. As expected, viral pathogens were associated with a decrease in OPV immunogenicity. Moreover, recently acquired viral infections appeared to inhibit OPV response to a greater extent than persistent viruses. Together, these findings have substantiated the inhibitory effect of viral pathogens on OPV response, while implicating bacterial pathogens as a potential risk factor for OPV failure in early infancy. Risk factors for rotavirus vaccine failure remain elusive.
15
Luiz, Wilson Barros. "Vacinas de administração oral contra diarréia associada à Escherichia coli enteropatogênica baseada em linhagens geneticamente modificadas de Bacillus subtilis." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42132/tde-19052010-150539/.
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O objetivo deste trabalho foi a construção de linhagens geneticamente modificadas de B. subtilis capazes de expressar porções de intimina, principal componente envolvido na capacidade de colonização de linhagens enteropatogênicas de Escherichia coli (EPEC), como estratégia vacinal de administração oral contra diarréias infecciosas. As vacinas desenvolvidas empregaram cinco regiões da intimina de EPEC e linhagens de B. subtilis capazes de expressar e acumular proteínas recombinantes no citoplasma. Além disso, avaliamos o uso de esporos e células vegetativas como veículos vacinais para a entrega de antígenos recombinantes a partir de sistema de expressão epissomal. A eficácia do modelo vacinal foi demonstrada pela: (i) produção de anticorpos sistêmicos (IgG) e secretados (sIgA) contra intimina, (ii) capacidade de neutralização das intiminas expressas por diferentes linhagens de EPEC pelos anticorpos específicos gerados nos animais imunizados; e (iii) proteção a desafio com linhagens de EPEC a partir de modelo experimental que emprega camundongos recém-nascidos. Os resultados representam uma etapa importante na validação de uma nova estratégia vacinal para o controle de patógenos entéricos. Além disto, propomos a utilização de um modelo animal como uma nova ferramenta para se avaliar o potencial protetor de vacinas contra EPEC.The objective of this work was the construction of genetically modified strains of B. subtilis able to express portions of intimin, the main component involved in colonization by enteropathogenic Escherichia coli strains (EPEC) as a strategy of oral vaccination against infectious diarrhea. The vaccines employed five regions of EPEC intimin and B. subtilis strains expressing recombinant proteins in the cytoplasm. Furthermore, we evaluated the use of spores and vegetative cells as vaccine vehicles for the delivery of recombinant antigens based on an epissomal expression system. The efficacy of the vaccines was demonstrated by: (i) production of systemic (IgG) and mucosal (sIgA) antibody responses to intimin, (ii) neutralizing of intimin expressed by different strains of EPEC by the antibodies generated in immunized animals, and (iii) protection to lethal challenges carried out with EPEC strains using an experimental model based in newborn mice. The results represent an important step in the validation of a new vaccine strategy for the control of enteric pathogens. Moreover, we propose the use of an animal model as a new tool to evaluate the protective potential of vaccines against EPEC.
16
Foulquier, Christine. "La vaccination par voie orale." Paris 5, 1996. http://www.theses.fr/1996PA05P179.
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Mann, Jamie Ferguson Sajjan. "Oral vaccine delivery using lipid vesicles." Thesis, University of Strathclyde, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431816.
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Klimovich, Charlotte Marie. "Investigations into the physiological and biomechanical basis of differential success in oral rabies vaccination between skunks (Mephitis mephitis) and raccoons (Procyon lotor)." Ohio University Honors Tutorial College / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1502454684921845.
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Chen, Hongming. "Polymerized liposomes as potential oral vaccine delivery vehicles." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/10343.
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Bennett, Ewan Murdoch. "Optimisation and mechanistic assessment of an oral influenza vaccine." Thesis, University of Strathclyde, 2010. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=25983.
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The aim of this thesis was to improve the formulation processes of an existing oral vaccine delivery system, the bilosome, and to investigate its mechanism of action. There were three main areas of research; (1) refinement and adaptation of the existing homogenisation melt method, (2) development of a new formulation process, and (3) investigation of the mechanism of action. The results from (1) showed that lyophilisation has no detrimental effect on the bilosome, allowing improved storage characteristics; this was proven in a 9-month study which showed that the immunogenicity of the lyophilised formulation was retained after this time. With a view to developing a system which could be more easily mass produced,a new formulation process using a microwave reactor was developed in (2). This gave bilosomes with equal immunogenicity to those in (1), in fewer steps and 1/5th of the time; these also allowed incorporation of inexpensive surfactants, which was not possible with the original method. As the formulation process had been successfully streamlined, the mechanism of action was examined in (3). It was thought that further understanding of this could provide information which would allow enhancement of the bilosomes immunogenicity. Results showed that no enhancement of immunogenicity was possible using bilosomes incorporating squalene, or with suppression of gastric acid pre-administration. Investigation of uptake in the intestine showed uptake in both the villi and the Peyer’s patches of the small intestine,which may prove useful in the development of future vaccine delivery systems. The study in the lungs was less successful, and a number of issues meant that no significant conclusions could be made; however, the groundwork has been laid for future work in this area.
21
Robin, Fabrice Fisch Alain. "Diarrhée du voyageur et vaccin anticholérique oral." Créteil : Université de Paris-Val-de-Marne, 2008. http://doxa.scd.univ-paris12.fr:80/theses/th0487171.pdf.
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Callaghan, Maximilian W. "Chimeric orthohepadnavirus core particles for oral delivery of vaccines: Part I. Transformation of tobacco plants with a gene encoding a c-terminus truncated hepatitis B virus core protein. Part II. Construction of a woodchuck hepatitis virus core protein-based universal epitope carrier and test expression in Escherichia coli." Thesis, University of Ottawa (Canada), 2001. http://hdl.handle.net/10393/9404.
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Recombinant hepatitis B virus (HBV) core particles have been successfully used as particulate carriers exposing viral and bacterial antigens on their surface. The objective of this research was to explore the use of recombinant core particles from HBV and its close relative the woodchuck hepatitis virus for edible vaccine technology. This was accomplished in two parts. Part 1 was the transformation of a truncated HBV core protein gene into transgenic tobacco plants and characterization of the gene's expression with respect to mRNA levels, protein levels, and particle self-assembly. Part 2 was the construction of a "universal antigen carrier" based on the woodchuck hepatitis virus (WHV) core protein and generation and characterization of chimeric WHV core proteins carrying two different epitopes from the hepatitis C virus (HCV) core protein. In conclusion, it appears that a different approach may be required to express core proteins from HBV-like viruses in transgenic tobacco plants. (Abstract shortened by UMI.)
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Rafati, Hassan. "In vitro and in vivo characterisation of biodegradable microparticles for vaccine delivery." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338533.
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Cary, Jewel Maria. "Development of a Nanoparticle Vaccine Delivery System with Polymeric Oral Adjuvants for Poultry." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/102504.
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Development of new vaccination technology has been hindered by a lack of new adjuvants to enable development of protective immunity using different vaccine delivery methods. A vaccine delivery system using oral adjuvants would be applicable across species for both individual and mass vaccination in both the medical and veterinary fields. We sought to create an oral nanoparticle (NP) vaccine delivery system that is easy to produce and uses polymers as oral adjuvants with killed virus. Our hypothesis was gelatin and chitosan would enhance viral uptake and stimulate immune cells to produce protective immunity. This would allow the safer killed form of each virus to be used in place of modified live (MLV) viruses and avoid undesirable side effects like immunosuppression. The research objectives were to
1. Fabricate and characterize gelatin NPs encapsulating inert materials of similar size and shape to the viruses of interest for fabrication proof-of-concept
2. Modify the NP delivery system to minimize immune cell cytoxicity for the vaccine delivery application
3. Fabricate and characterize FPV and HEV viral nanoparticles' stability, cellular uptake/infectivity, and released viruses' ability to replicate
4. Compare the abilities of the killed HEV nanovaccine, killed HEV with loose gelatin and chitosan polymers (no nanoparticle), and a live HEV commercial vaccine to induce textit{in vivo} seroconversion, protective immunity, and side effects during clinical and challenge studies in turkeys
We proved our hypothesis to be correct in addition to demonstrating matching the encapsulation material size to empty NP size leads to preferred encapsulated NP formulation parameters, chitosan stabilizes the NP formulation bypassing the need for cytotoxic crosslinkers, and paraformaldehyde is able to kill virus prior to vaccine formulation while still preserving virus morphology sufficiently for immune cell recognition. This development constitutes one of the first novel adjuvants discoveries in 70 years and opens the door for conversion of injectable vaccines to oral delivery across species.Doctor of Philosophy
25
Limpanussorn, Jakkrapong. "Aspects of persorption : quantification, location, dissemination and the influence of immunosuppression." Thesis, Queen Mary, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300181.
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Yeh, Ming-Kung. "Biodegradable microparticles as delivery system for proteins and peptides." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319677.
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Pavlov, Dobromir Nikolov. "Genomic mutations in oral poliovirus vaccine strains implications for the eradication of poliovirus /." Pretoria : [s.n.], 2004. http://upetd.up.ac.za/thesis/available/etd-11172005-120800.
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Pavlov, D. N. (Dobromir Nikolov). "Genomic mutations in oral poliovirus vaccine strains : implications for the eradication of poliovirus." Thesis, University of Pretoria, 2004. http://hdl.handle.net/2263/29511.
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Large epidemics of poliomyelitis spread across the world in the first half of the 20th century. However, polio incidence fell rapidly across the world following the introduction of the oral poliovirus vaccine (OPV). Since the introduction of immunisation with OPV, the vaccine had a remarkable track record of success, because the number of wild-type polio cases decreased from 350 000 to 500 and the number of polio endemic countries declined from 125 to 10. Thus, the global eradication of wild-type poliovirus (PV) seems a realistic goal for the foreseeable future. Despite its many advantages, one disadvantage of the OPV is the potential risk of revertants of the OPV strains, which may cause neurological complications in vaccine recipients and susceptible contacts. Immunocompetent persons excrete OPV strains for a limited period of time. In contrast, immunodeficient people may become chronically infected and excretion times as long as 10 years have been reported. As a consequence, in the last phase of polio eradication this group of people may serve as potential reservoirs for vaccine-derived polioviruses (VDPVs). Two cases of vaccine-associated paralytic poliomyelitis have been reported in human immunodeficiency virus (HIV)-positive children, although, presently there is no evidence for prolonged excretion of PV from patients with HIV and acquired immunodeficiency syndrome (AIDS). Highly evolved VDPVs have been isolated from sewage and river water even in the absence of cases of paralytic poliomyelitis. This study aimed to investigate the prevalence of PVs in sewage and river water as well as in stool specimens of HIV-positive children (including those with an AIDS indicator condition according to the Centers for Disease Control and Prevention classification). Secondly, the study investigated the occurrence of genomic mutations in these OPV isolates. A total of 49 PV vaccine strains were isolated from the sewage and river water, and 13 PV vaccine strains were detected in the stools of immunodeficient children. Two of the immunodeficient patients (vaccinated 15 months ago) tested positive for Sabin PVs type 1 and 3. Another immunodeficient patient (vaccinated 42 months ago) tested positive for Sabin PV type 1. The 5’untranslated and the VP1 regions in the genomes of the OPV isolates were partially sequenced. The majority of the OPV strains detected in the sewage and river water displayed >99% VP1 sequence identity to the original PV vaccine strains and were classified as “OPV-like viruses”. Two OPV isolates were identified as “suspected” VDPVs, since these isolates showed £99% VP1 sequence identity to the PV vaccine strains and had probably replicated in one or more people for 12 to 16 months since the administration of the initiating OPV dose. In contrast, three “suspected” immunodeficient VDPVs were identified in the stools of the immunodeficient children. All of the OPV-like and “suspected” VDPV isolates carried genomic mutations, which had been associated with reversion of the attenuated PV phenotypes to increased neurovirulence. The identification of OPV-like and “suspected” VDPVs in this study emphasised the fundamental importance regarding the control of health risks constituted by OPV vaccination, particularly with regard to immunodeficient individuals such as HIV-positive children, and the possible role of water in the transmission of potentially hazardous VDPVs. These research findings provided valuable data, concerning prolonged excretion of OPV strains by individuals with secondary immunodeficiency and this could have major implications for strategies aimed for the global post-polio eradication era.Thesis (PhD (Medical Virology))--University of Pretoria, 2004.
Medical Virology
unrestricted
29
Breau, Cathy. "Development of an oral recombinant chancroid vaccine delivered by attenuated Salmonella typhimurium SL3261." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28079.
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Chancroid, a sexually transmitted genital ulcer disease caused by the Gram-negative bacterium Haemophilus ducreyi, facilitates the acquisition and transmission of H1V. An effective vaccine against chancroid has yet to be developed. We hypothesize that a Salmonella vector-based vaccine, expressing H. ducreyi antigens, could confer protective immunity in the rabbit model of H. ducreyi infection. The H. ducreyi outer membrane hemoglobin receptor HgbA has been shown to be a suitable vaccine candidate. HgbA was expressed from S. typhimurium SL3261 (pnirBhgbA) but not from the control strain, S. typhimurium SL3261 (pnirB). After a single dose or three doses, at two-week intervals of the vaccine, no antibody response to HgbA was detected in the rabbit model. The vaccine administered was immunogenic and survived in vivo passage. In this small animal trial, we were unable to induce protective immunity against chancroid. We conclude that the vaccine does not confer protective immunity against chancroid.
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Kostrzak, Anna. "Les pseudo-particules virales du VHB, produites chez les plantes, comme vecteur d'un polyépitope du VIH-1 pour un vaccin oral bivalent contre le sida et l'hépatite B." Versailles-St Quentin en Yvelines, 2009. http://www.theses.fr/2009VERS0042.
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Actuellement un des besoins vaccinaux les plus importants est de trouver un moyen d'immunisation efficace et économique contre l'hépatite B et d'autres maladies touchant les pays en voie de développement. Les plantes transgéniques pourraient être une source alternative simple, efficace et bon marché des composants du vaccin, ne nécessitant pas un personnel médical hautement qualifié pour l'administration. Nous avons obtenu les plantes transgéniques du tabac contenant la séquence codant le petit antigène de surface du VHB-SHBsAg. Le niveau d'expression de SHBsAG a été vérifié par le test immunoenzymatique ELISA, et la capacité de former des pseudo-particules virales (VLPs) a été confirmée indirectement par western blot et directement par microscopie électronique à transmission. Les plantes caractérisées par un haut niveau d'expression de la protéine SHBsAg ont été lyophilisées et le matériel vaccinal obtenu a été utilisé pour l'immunisation orale de souris "humanisées" dans le but d'étudier une réponse spécifique cellulaire par stimulation des lymphocytes T CD8+ et de déterminer le niveau des lymphocytes Treg dans les ganglions lymphatiques et la rate, ainsi que la réponse humorale par l'analyse du niveau des anticorps sécrétés IgA (S-IgA), des IgA et IgC dans le sérum. Les plantes de tabac non transgéniques et les plantes SHBsAg choisies ont été utilisées pour la retransformation avec les vecteurs modifiés pCAMBIA contenant les séquences codant les protéines de fusion PE-SHBsAg composées du polyépitope du VIH-1 et de SHBsAg. Les données obtenues élargissent la connaissance sur l'utilisation des pseudo-particules virales du VHB comme porteurs d'épitopes du VIH-1 exprimant les protéines polyépitope-SHBsAg chez les plantes, sur la retransformation des plantes, et sur l'immunisation orale par le matériel vaccinal d'origine végétaleCurrently one of the most important worldwide demands is to find a more efficacious, cost-effective and reliable method of mass immunization for hepatitis B and many other fatal diseases afflicting underdeveloped regions of the globe. Plants plants could potentially symplify, and thus lower, the cost of immunization and by obviating the need for needles and specialized medical staff. We obtained the transgenic tobacco plants expressing small hepatitis B antigen (SHBsAg). The production and structure of SHBsAg was measured by anti-SHBsAg ELISA, western blot and transmission electron microscopy. Transformants showing high SHBsAg expression were lyophilized and the immunogenicity of dried leaves containing SHBsAg was evaluated by measuring cellular and humoral responses. For the cellular response, we measured the activation of CD8 T cells and the presence of T regulatory cells (Tregs) in peripheral lymph nodes and spleen. The humoral response was evaluated by ELISA tests, measuring anti-SHBsAg IgGs in serum and anti-SHBsAg IgAs in faeces and serum. Non-transgenic tobacco plants and plants producing SHBsAg were used for genetic transformation with three different constructs containing an HIV polyepitope-SHBsAg fusion protein. These results brings new knowledge in the use of the Hepatitis B virus-like particles as carrier of an HIV-1 polyepitope in palnts, second genetic plant transformation and plant oral immunization
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Cuervo, Nancy Stella. "Variabilité des souches vaccinales de poliovirus par recombinaison génétique." Paris 11, 2001. http://www.theses.fr/2001PA114820.
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Stertman, Linda. "Starch Microparticles as an Oral Vaccine Adjuvant with Emphasis on the Differentiation of the Immune Response." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ-.bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4680.
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Han, Yi. "Development and Evaluation of Mucoadhesive Chitosan Nanoparticle-based Salmonella Vaccine for Oral Delivery in Broiler Birds." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587571015936815.
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Pettit, Wendy Marie. "Towards the development of a multicomponent, nanoscale oral vaccine delivery system targeting infectious bursal disease (IBD)." Thesis, University of Greenwich, 2013. http://gala.gre.ac.uk/11376/.
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As the global population increases, estimated to reach 9 billion by the year 2050, global food security becomes a priority. A prominent disease implicated in financial loss to the poultry industry, on a global scale, is infectious bursal disease virus (IBDV). Vaccination against IBDV is sub-optimal and difficult to deliver. Therefore it has been highlighted as a key area for the development of an oral vaccine. A highly conserved capsid protein from IBDV (VP2) was identified, and sub-cloned into a bacterial expression cassette. This protein was fused to a potential carrier protein (cholera toxin B chain), previously shown to mediate the exit from the gut lumen into the lamina propria. However, to allow this antigen to reach the mucosal associated lymphoid tissue, the protein antigen must remain in its native conformation through the stomach. This work developed a delivery system to meet this end. By encapsulation within a fatty acid coated, protein adsorbed-solid core drug delivery system (SCDDS), it was shown that a model protein antigen (GST-GFP) could be protected from low pH (i.e. pH 2.0) and proteases. Protease protection was demonstrated against the exposure of myristic acid coated, GST-GFP adsorbed silica, to both protease K (100 μU, 1hour (100% protection)) as well as a simulated in vitro stomach environment (pepsin (0.2 mg) (100% protection)). Having demonstrated protection from proteases at pH 2.0 and pH7.4, it was then shown that GST-GFP could be released from the myristic acid coated silica at pH 8.8 (consistent with the small intestine). As much as ~15% (15 μg) (w/w) GST-GFP was released from the aforementioned system. The evidence supporting this conclusion was drawn from molar ellipticity calculations that showed the proportion of helical structure in relation to regions of beta sheet remained constant, pre-adsorption and post-release (16.9% α-helix, 20.8% β-sheet, 43.3% random coil). Finally, this work has shown that if a recombinant antigen was fused to cholera toxin B chain (but not shiga toxin B chain), it was capable of mediating transcytotic passage across, differentiated, polarised Caco-2 cells (1/1000th input (10 ng)). In conclusion and based upon the evidence provided above, this system warrants further optimisation and investigation to serve as an oral vaccine delivery system to treat IBDV.
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Berardi, Alberto. "An investigation into the use of a plant-expressed virus-like particle as an oral vaccine candidate." Thesis, University of East Anglia, 2013. https://ueaeprints.uea.ac.uk/47928/.
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Plant-expressed virus-like particles (VLPs) could offer an alternative method for the oral delivery of vaccines. VLPs' robustness, combined with their compartmentalisation within the plant cells, should favour their stability in the harsh gastro-intestinal (GI) environment. In the small intestine, intact VLPs should be available for absorption by the Follicle-associated epithelium (FAE), considered the main portal of entry for antigens in the gut. In this work, Hepatitis B core antigen (HBcAg) VLPs, expressed transiently in Nicotiana benthamiana leaves, were extracted, purified and characterised. The stability of purified HBcAg VLPs in simulated human gastric and intestinal media was investigated. The results suggested that the antigen was unstable when subjected to various simulated gastric fluids. Upon incubation in simulated human and ex vivo pig intestinal fluids, HBcAg maintained higher stability. Leaves expressing HBcAg VLPs could be dried, retaining good antigen stability, but the natural encapsulation in the leaves failed to protect the antigen from degradation in the simulated GI fluids. However, enteric-coated “green” tablets containing dried leaves expressing HBcAg could be produced and were shown to confer protection in simulated gastric fluids but allowed the release of intact antigen in simulated intestinal fluids. Purified HBcAg VLPs could be formulated into spray-dried and spray freeze-dried microparticles using a pH-responsive polymer. However, such formulations showed poor gastro-resistance, negating their use for targeted intestinal delivery. HBcAg VLPs could be also freeze-dried, suggesting the potential use of freeze-drying for further processing of the antigen into an oral formulation. A human cell culture model of the small intestinal epithelium indicated selective absorption of HBcAg VLPs by the FAE but limited overall absorption. In vivo ligated loop studies in mice suggested poor intestinal absorption, mainly relegated to the FAE. This research represents an original investigation into the possible applications of plant-expressed HBcAg VLPs for oral drug delivery.
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Durbin, Michael A. "The effects of an oral furunculosis vaccine on the immune system of rainbow trout (oncorhynchus mykiss, Walbaum)." Thesis, Heriot-Watt University, 1997. http://hdl.handle.net/10399/704.
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Coulson, Nicholas Michael. "Expression of the protective antigen of Bacillus anthracis in attenuated Salmonella : a potential of oral anthrax vaccine." Thesis, University of Warwick, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359929.
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Pollock, Louisa Elizabeth. "Predictors of vaccine virus replication, immune response and clinical protection following oral rotavirus vaccination in Malawian children." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3022905/.
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Background: Current rotavirus vaccines are least effective in low-income, high-burden countries. Reduced vaccine response is likely to be multifactorial. The aim of this thesis was to determine whether passively-acquired maternal antibody levels, oral polio vaccine (OPV) response and histo-blood group antigen (HBGA) phenotype predict vaccine virus replication, immune response and clinical protection in Malawian infants following oral administration of the monovalent human rotavirus vaccine (RV1). Methods: In a longitudinal cohort study, infants received two doses of RV1 at 6 and 10 weeks of age. Stool was collected on alternate days for 10 days post-vaccine to detect RV1 and OPV vaccine virus shedding by RT-PCR. Pre and post-vaccine serum rotavirus(RV)-specific IgA and IgG were determined by ELISA, with seroconversion defined as change from seronegative (RV-specific IgA < 20 u/mL) to seropositive (RV-specific IgA > 20U/mL) or > 4x rise in concentration in infants seropositive at baseline. HBGA phenotype was determined by salivary ELISA and confirmed by FUT2 genotyping. Infants with detectable of A, B, or H antigens in saliva were defined as secretors. Infants with detectable Lewis a or b antigens in saliva were defined as Lewis positive and those with undetectable Lewis antigens as Lewis negative. In a separate cross-sectional case-control study, vaccinated infants < 12 months with rotavirus gastroenteritis (RVGE) were compared to age-matched, vaccinated community and non-RVGE controls. Rotavirus detection and genotyping were confirmed by RT-PCR. Results: Following rotavirus immunisation, 104/202 (52%) of infants had detectable vaccine virus shedding and 47/196 (24%) achieved RV-specific IgA seroconversion. Infants with the highest levels of maternal rotavirus-specific IgG antibody had reduced likelihood of vaccine virus shedding (RR 0.44, 95%CI 0.27-0.72, p=0.001) and lower RV-specific IgA response. Linear correlation between RV-specific IgG and vaccine response was weak, suggesting a threshold effect. There was no correlation between quantitative rotavirus and OPV vaccine virus shedding, but some evidence of common patterns of OPV and RV1 response. Protective poliovirus type 3 neutralizing antibody titres at 6 weeks were associated with RV1 shedding in the 1st RV1 dose period (RR 2.24, 95%CI 1.25-4.0, p=0.007). OPV shedding in the 2nd RV1 dose period was associated with RV1 shedding (RR 2.0, 95%CI 1.0-3.8, p=0.04). All 14 infants who failed to attain protective serotype 3 poliovirus-specific neutralizing antibody titres also failed to attain rotavirus vaccine seroconversion. There was no association observed between any HBGA phenotype and overall likelihood of vaccine virus shedding or seroconversion. In a sub-study of 186 infants, HBGA phenotype determined genotype-specific susceptibility to rotavirus infection: secretor phenotype was strongly associated with P[8] RVGE (OR 7.8, 95%CI 1.8-33.7, p=0.005) and P[4]RVGE (OR 5.8. 95%CI 1.3-25.2, p=0.02) and Lewis negative phenotype was associated with P[6] infection (OR 3.0, 85%CI 1.3-6.7, p=0.008). Comparing 119 RVGE cases to 119 age-matched community controls, non-secretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure (OR 0.40, 95%CI 0.2-0.8, p=0.005). RV-specific IgA > 90U/mL at time of presentation was associated with a 75% decrease in the odds of clinical vaccine failure. Infants with vaccine failure mounted a robust convalescent RV-specific IgA response. Conclusions: A threshold inhibitory effect of maternal antibody, together with the strong association of low RV-specific IgA and vaccine failure, suggests that booster dosing regimens could potentially improve RV1 effectiveness in Malawi. Further research is required to determine the optimal schedule. There was no evidence of direct competitive inhibition observed between OPV of RV1 vaccine virus shedding patterns. Common factors may predict response to both vaccines. Contrary to our hypothesis, non-secretor infants were at decreased risk of clinical vaccine failure, due to relative protection against common rotavirus strains. HBGA phenotype is unlikely to contribute to reduced rotavirus vaccine effectiveness in Malawi. New non-P[8] based vaccines are therefore unlikely to confer additional benefit based on the HBGA hypothesis.
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Mandal, Amitesh. "Modification of a DNA Vaccine for Oral Administration in Fish for Aquaculture by Using Non-Microbial Nanoparticles." Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/33576.
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Utilization of DNA vaccines in aquaculture has been gaining interest and recent efforts have been focused on methods of delivering DNA vaccines to fish. In the present study, a methodology was sought that could protect DNA vaccines such that they could be orally administered. The main objective of the study was to determine if a DNA vaccine could be effectively compounded into an orally administrable formulation with chitosan or polylactide-co-glycolide (PLG). The immune response of hybrid striped bass (Morone saxatilis x Morone chrysops) following oral delivery of a DNA vaccine containing Mycobacterium marinum Ag85A plasmid in either chitosan or PLG nanoparticle encapsulation was evaluated. Hybrid striped bass were divided into four experimental groups: IM immunization of the DNA vaccine as a positive control, oral delivery of uncomplexed DNA vaccine, oral delivery of chitosan or PLG alone as a negative control, and oral delivery of complexed chitosan or complexed PLG DNA vaccine. Fish were bled at regular intervals and an ELISA was used to evaluate antibody levels in individual fish. While the chitosan /plasmid DNA complex containing the Mycobacterium marinum Ag85A gene failed to produce a significant antibody response, the PLG/plasmid DNA matrix stimulated humoral immune response in the fish.Master of Science
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Rakoto, Andrianarivelo Mala. "Emergence de souches de poliovirus recombinantes dérivées du vaccin polio oral à Madagascar." Paris 5, 2005. http://www.theses.fr/2005PA05N03S.
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Les entérovirus humains comprennent 5 espèces virales et notamment les entérovirus du groupe C (11 sérotypes de coxsackievirus A, CAV) et les poliovirus (3 sérotypes). Ces derniers sont les agents de la poliomyélite, une maladie prévenue grâce à deux vaccins, un vaccin inactivé et un vaccin oral (VPO) constitué de souches atténuées. Le VPO est utilisé extensivement pour éradiquer la maladie. Le travail de cette thèse a constitué à étudier les effets de la vaccination avec ce vaccin sur la réponse humorale et la circulation de souches virales à Madagascar. Nous avons ainsi mis en évidence que des souches de poliovirus d'origine vaccinale (VDPV) étaient à l'origine de l'épidémie de poliomyélite survenue en 2001-2002. Ces VDPVs portaient par ailleurs, des séquences d'entérovirus inconnus, sûrement des CAV du groupe C. Nous avons alors, étudié la circulation des entérovirus surHuman enteroviruses include 5 viral species and, in particular, species C enteroviruses (11 serotypes of coxsackievirus A, CAV) and polioviruses (3 serotypes). Polioviruses are the pathogenic agents of poliomyelitis. This disease can be prevented with the use of two vaccines, the inactivated polio vaccine and the oral polio vaccine (OPV) which is made up of attenuated strains. OPV is extensively used to eradicate poliomyelitis. The aims of this work were to study the immune response to OPV and the circulation of enterovirus strains in Madagascar. We have shown that the outbreak of poliomyelitis wich has occurred in 2001-2002 had been caused by vaccine-derived poliovirus (VDPV). Part of the genomes of these VDPVs was derived from unknown non-poliovirus enterovirus that were thought to be species C enteroviruses
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Silva, Camila Sloboda Pacheco da. "Desenvolvimento de vacina anti-rábica oral testada em camundongos = Development of an oral rabies vaccine tested in mice / Camila Sloboda Pacheco da Silva ; orientador, Rüdiger Daniel Ollhoff." reponame:Biblioteca Digital de Teses e Dissertações da PUC_PR, 2011. http://www.biblioteca.pucpr.br/tede/tde_busca/arquivo.php?codArquivo=2234.
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Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, São José dos Pinhais, 2011Inclui bibliografias
A raiva permanece como uma doenca preocupante para medicos e veterinários devido aos expressivos prejuizos e perdas que ela acarreta. O estudo continuado da raiva, focando em seus metodos profilaticos e em especial no desenvolvimento de novos metodos vaci
Rabies remains a preoccupying disease in human and animal medicine due to the expressive losses that it causes. The continued study of rabies, concentrating on its prophylactic methods, specifically in the development of new vaccine methods becomes essent
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Sevil, Victoria. "Influence of oral boost immunizations with recombinant Salmonella vaccine strains on the antigen-specific CD8 T-cell induction." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-72867.
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Rydell, Niclas. "Development of a New Oral Vaccine against Diphtheria and the Study of its Immunogenicity in Mouse and Man." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4629.
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Delph, Katherine. "Comparison of immunologic responses following intranasal and oral administration of a USDA-approved, live-attenuated Streptococcus equi vaccine." Thesis, Kansas State University, 2016. http://hdl.handle.net/2097/32595.
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Master of ScienceDepartment of Clinical Science
Elizabeth Davis
Background: While there is a commercially-available vaccine for Streptococcus equi subsp. equi licensed for the intranasal route of administration, some equine practitioners are administering this vaccine orally despite a lack of evidence for its efficacy by this route of administration. Objectives: To compare systemic and local immune responses following intranasal or oral administration of the USDA-approved, live-attenuated Streptococcus equi subspecies equi vaccine (Pinnacle IN®, Zoetis, Florham Park, New Jersey). Study Design: Experimental, randomized clinical trial Methods: Eight healthy horses with low Streptococcus equi M protein (SeM) titers (<1:1600) were randomly assigned to an intranasal or oral two-vaccine series. SeM-specific serum immunoglobulins G (IgG) and A (IgA) and nasal secretion IgA were assessed using a commercially-available ELISA (Equine Diagnostic Solutions, LLC, Lexington, Kentucky) and a novel magnetic microsphere assay utilizing fluorescence. A general linear mixed models approach was used for statistical data analysis. Results: As expected, intranasal vaccinates showed substantial increases in both serum SeM-specific IgG and IgA levels post-vaccination (P=0.0006 and P=0.007, respectively). Oral vaccinates showed an increase in serum SeM-specific IgG post-vaccination (P=0.0150), though only one-third the magnitude of intranasal vaccinates. Oral vaccinates showed no evidence of change in SeM-specific IgA post-vaccination (P=0.15). Main Limitations: Changes in mucosal antibody responses were not identified in this study which may be related to small change in antibody response, timing of sample collection, or method of nasal secretion collection. Conclusions: Results indicate that intranasal or oral vaccine administration resulted in increased serum SeM-specific IgG, though the magnitude of response differed between routes.
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Revaud, Julien. "Les mécanismes impliqués dans la mise en place de la réponse immunitaire dans le cadre d'une administration par voie orale de vaccins vectorisés dérivés des adénovirus et effets des adjuvants." Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC028.
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Le développement de nouveaux vaccins administrables par voie orale est un objectif important. De tels vaccins permettraient l'induction de réponses immunitaires au niveau des muqueuses, qui constituent les principales voies d'entrée des agents pathogènes dans l'organisme, et seraient plus pratiques et plus sûrs pour l'Homme. La voie orale est aussi la voie la plus adaptée à la vaccination de la faune sauvage. À l'heure actuelle peu de vaccins sont administrés par voie orale et la plupart sont des vaccins vivants atténués, qui présentent certains risques. Les vaccins vectorisés non réplicatifs dérivés des adénovirus (VVA) représentent une alternative attractive. Ils sont plus sûrs et sont très efficaces lorsqu'ils sont administrés par voie parentérale. Néanmoins, leur efficacité est diminuée après administration par voie orale. Les objectifs de ce travail se divisent en trois points : 1. Comprendre les différentes étapes de mise en place de la réponse immunitaire après une administration par voie orale d'un VVA. 2. Explorer diérentes stratégies d'optimisation de ces vaccins. 3. Déterminer l'impact des adjuvants sur les étapes précoces de-mise en place de la réponse Immunitaire. Par des techniques utilisant la bioluminescence et la RT-PCRq, nous avons montré qu'après une administration par voie infra-gastrique d'un VVA chez deux souches de souris (C57BL/6 et BALB/c), l'expression du transgène était restreinte à l'intestin et limitée à certaines régions anatomiques. Nous avons également évalué l'action de plusieurs adjuvants sur les réponses immunitaires induites par les VVA par voie orale ainsi que leurs eets sur l'expression du transgène Chez les souris C57BL/6 et BALB/cThe development of new vaccines for oral delivery is a desirable objective. Such vaccines would permit induction of immune responses at mucosal surfaces, which constitute the principal portais of entry for pathogens. Moreover, the oral delivery route, as compared with parenteral routes, would be safer and more practical for human usage, and would facilitate the vaccination of wildlife. At present, bowever, few vaccines are administered by die oral route. Of these, most are live attenuated vaccines, which present a certain risk. Non-replicative vectored vaccines derived from adenoviruses (rAd) tepresent an attractive alternative, as they are much safer than live attenuated vaccines and are capable of eliciting robust immune responses when delivered by parenteral routes. Nevertheless, their efficacy is diminished upon oral administration. The objectives of this study were three-fold : 1. To understand the different steps leading to induction of an immune response after oral delivery of rAd, 2. To explore different strategies for optimisation of such vaccines, 3. To determine the impact of adjuvants on the early steps involved in the induction of the immune response. After intragastric delivery of rAd, we measured transgene activity by bioluminescence and RT-qPCR, and showed that transgene expression was confined to the intestine, and restricted to delimited anatomical zones. Moreover, the distribution of bioluminescence and antigen-encoding transcripts was dissimilar in C57B1/6 and BALB/c mice. Finally, after intragastric delivery of rAd, we showed that adjuvants affect transgene expression and the ensuing immune response in both C57BL/6 and BALB/c mice
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Blanc, Charlotte. "Lymphocytes T résidents mémoires dans les tumeurs du poumon et ORL : sous-populations et mécanismes de migration Cxcr6-deficiency impairs cancer vaccine efficacy and resident memory CD8+ T cells recruitment in tumor Phénotype et localisation des sous-populations de LT résidents mémoires dans les tumeurs pulmonaires." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB046.
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De grands bouleversements sont apparus au début du 21ème siècle dans la compréhension de la physiopathologie du cancer avec l'énoncé de la théorie de l'immunoédition complétant le concept de l'immunosurveillance. La communauté scientifique s'accorde désormais sur le fait que le système immunitaire et particulièrement les lymphocytes T (LT) CD8+ tiennent une place essentielle dans le contrôle de la croissance tumorale. Toutefois, par pression de sélection, la cellule tumorale développe des mécanismes de résistance aux attaques du système immunitaire, neutralisant ainsi l'effet cytotoxique des LT. Restaurer leurs fonctions antitumorales est une stratégie thérapeutique qui a fait ses preuves avec l'immunothérapie. Cependant, ces traitements ne sont pas toujours efficaces et peuvent être optimisés par une meilleure compréhension de l'immunité antitumorale. Dans ce but, nous nous sommes intéressés au déroulement de la réponse antitumorale des LT CD8+ en nous attardant sur les LT résidents mémoires (Trm) particulièrement efficaces contre la tumeur et au fort impact pronostic, qui pourrait être une cible thérapeutique pertinente. L'induction d'une réponse antitumorale efficace requière une présentation antigénique optimale conduisant à l'activation du LT CD8+ et à sa migration dans la tumeur via le réseau chimiokine/récepteur. Dans le premier travail, le récepteur de chimiokine CXCR6 a été identifié comme molécule de homing fortement exprimée par les LT CD8+ Trm du poumon. Sa chimiokine CXCL16 peut être sécrétée par les cellules présentatrices d'antigènes, les cellules épithéliales et tumorales mais le rôle de l'axe CXCR6/CXCL16 dans l'immunosurveillance des cancers n'est pas connu à ce jour. Pour en comprendre les mécanismes, des expériences de vaccinations antitumorales par voie intranasale (i.n.) réalisées dans des modèles de souris déficientes en CXCR6 ont permis de mettre en évidence l'impact de CXCR6 dans l'établissement d'une infiltration optimale en LT CD8+ spécifiques et Trm dans le lavage broncho-alvéolaire et au sein des tumeurs des voies aérodigestives supérieures. L'axe CXCR6/CXCL16 pourrait représenter un outil thérapeutique intéressant pour les vaccins anticancéreux ou pour les thérapies de transferts adoptifs de LT modifiés dont l'infiltration intra-tumorale est limitée. Les Trm ont la particularité d'exprimer des intégrines (CD103, CD49a) impliquées dans leur interaction avec le microenvironnement tumoral. Ils présentent un phénotype original microenvironnement-dépendant qui leur confère des avantages en termes d'activités cytotoxiques dans les tumeurs et expliquant leur impact pronostic favorable. Une meilleure connaissance de leur phénotype et de leurs mécanismes d'induction permettrait d'optimiser la réponse antitumorale. Le travail 2 s'est concentré sur l'étude de deux intégrines principales CD103 et CD49a dans les cancers pulmonaires par des techniques multiparamétriques d'immunofluorescence in situ et de cytométrie en flux. Les résultats montrent que leur expression expliquait l'infiltration des LT CD8+ et leur contact avec la cellule tumorale, en lien avec leur forte implication dans la survie des malades. Nos données suggérèrent également la possibilité d'un priming local pulmonaire nécessaire à l'induction du phénotype Trm par des modèles de vaccinations i.n. et d'un lien entre les structures lymphoïdes tertiaires et les Trm. Ces travaux ont montré l'importance de l'analyse de l'immunité locale avec les LT CD8+ Trm pour la compréhension de cette réponse antitumorale. Etudier le phénotype Trm a permis de mettre en lumière leur rôle crucial et leur potentiel comme cible thérapeutique. Une meilleure connaissance des mécanismes sous-jacents à l'induction des Trm permettra à terme de les cibler pharmacologiquement pour optimiser les thérapies et donc la survie des maladesWith the immunoediting theory, new concept in the cancer physiopathology has appeared in the beginning of the 21st century. It is now established that the immune system and CD8+ T cells play a crucial role in tumor growth control. However, by selective pressure, the tumor cell develops mechanisms to avoid immune destruction and to inhibit T cells cytotoxicity. Reinvigorating antitumor functions is a well-proven therapeutic strategy with immunotherapy. Nevertheless, patients do not always respond to these treatments which could be optimized. In this context, we had studied antitumor response induction by focusing on CD8+ T cells and especially on resident memory T cells (Trm), new cytotoxic cells correlated with a good prognosis and which could be a relevant therapeutic target. A potent antitumor response requires an optimal antigenic presentation to prime CD8+ T cells and favor their migration into the tumor through chemokine network. In a first study, we identified a chemokine receptor CXCR6, highly expressed by lung CD8+ Trm. Its chemokine CXCL16 is produced by antigen presenting cells, epithelial and tumor cells, but the role of the CXCR6/CXCL16 axis in cancer immunosurveillance is not known yet. To understand its mechanisms, antitumor vaccinations strategies by intranasal (i.n.) route had been set up in CXCR6-deficient mice and had shown the role of CXCR6 in promoting the infiltration of specific CD8+ T cells and Trm in lung tissue and head and neck tumors. The CXCR6/CXCL16 axis could represent an interesting therapeutic tool for antitumor vaccines or adoptive cell transfer in which tumor infiltration is a challenge. Trm have the particularity to express integrins (CD103, CD49a) involved in the interaction with the tumor microenvironment. They exhibit an original and an heterogenous phenotype, microenvironment-dependent. Their phenotype is involved in their cytotoxic activities, highlighting their high prognostic impact and their potential to be a suitable therapeutic target. Better understanding Trm phenotype complexity and their induction mechanisms are crucial to further optimize antitumor response. The second work of this thesis focused on the expression of two main integrins CD103 and CD49a in lung cancer by an in situ multiparametric immunofluorescence technique and by flow cytometry. The results showed that their expression determine their contact with the tumor cells and their involvement in patient survival. Our data obtained by i.n. vaccination models and by tertiary lymphoid structures analysis suggest the possibility of a priming in the lung to induce the Trm phenotype. Our work shows the necessity of analyzing local immunity and CD8+ Trm T cells for a better understanding of antitumor response. Studying Trm phenotype has highlighted their crucial role and their potential to be a relevant therapeutic target. Identifying and targeting their mechanisms of induction might optimize therapies and patient's survival
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Colin, Henri. "Etude de l'action d'un vaccin ribosomal dans les gingivites et les parodontites." Paris 7, 1985. http://www.theses.fr/1985PA07F119.
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La première partie de ce travail est consacrée à une revue bibliographique des travaux concernant l'immunothérapie par voie orale. La deuxième partie relate l'expérimentation : un placebo et un vaccin composé de ribosomes bactériens associés à des protéoglycanes membranaires ont été administrés en double aveugle, pendant 21 jours, à 28 patients volontaires atteints de gingivite ou de parodontite. Des critères cliniques, histologiques, bactériologiques et immunologiques ont été utilisés pour tester l'action du vaccin. Le développement des défenses locales s'est principalement manifesté par l'augmentation notable de la production des IgA 11 S et des IgA spécifiques correspondant aux valences antigéniques constituant le vaccin, chez les sujets traités comparativement aux sujets placebo.
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Mallet, Laurent. "Analyse qualitative et quantitative des marqueurs moléculaires majeurs de la neurovirulence des poliovirus." Lyon 1, 1996. http://www.theses.fr/1996LYO1T195.
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Wong, George Kaon. "Development of novel oral enteric-coated aquaculture vibrio vaccines." Thesis, 1990. http://hdl.handle.net/1957/37467.
Full textAbstract:
An oral Vibrio vaccine for salmonids was developed.
The vaccine was produced by spray coating lyophilized
formalin-killed whole cells of Vibrio anguillarum (VA LS 1-
74) onto non-pareil sugar beads. Then methacrylic acrylic
acid copolymer (Eudragit L-30D) was applied as an enteric
protective coating.
Using x-ray radiographic techniques, it was found that
large particles (> 1.1 mm) remain in the fish stomach for
more than 2 hours before they would enter the pyloric caeca.
The pyloric sphincter which has an opening of 0.94 mm, acts
as barrier to prevent the passage of large food particles in
the stomach to the pyloric caeca. Based on this information
non-pareil sugar beads of 18-20 mesh or smaller should be
used as the vaccine carriers. A 15% (w/w) Eudragit L-30D
coating is needed to provide enteric protection of the
vaccine loaded sugar beads of 18-20 mesh size. Lower levels
of coating resulted in the bead breaking down in the stomach
and releasing contents prior to entering the pyloric caeca.
Since the lymphoid tissues are diffuse throughout the whole
GI tract, it may not be necessary to target a vaccine to
deliver antigens to a specific area of the intestinal tract,
but only protect the antigens from gastric fluids.
In vitro dissolution studies indicate that 10% VA LS 1-
74 loading was sufficient for rapid vaccine release (42%
released in 30 minutes) and a 15% Eudragit L-30D coating was
suitable for providing protection against stomach acid. The
vaccine product used in vivo studies contained 10% VA LS 1-
74 and 15% Eudragit L-30D on non-pareil sugar seeds of 18-20
mesh size.
Coho salmon were given the vaccine orally, and 30 days
afterward a live challenge test was performed. There was no
significant difference in the survival rates in a live
bacteria challenge test with the positive control (83.3%)
and test (80.3%) groups. Both had higher survival rates
than the no vaccine fed control group. The serum and
mucosal antibody levels to Vibrio were significantly higher
(p<0.01) in the test group (19700 units/ml) than the other
two groups (2530 units/ml in the positive control group and
617 units/ml in the negative control group). The antibody
titer appears to be a better indicator for vaccine efficacy
than survival rate of live bacteria challenge tests.
The oral Vibrio vaccine developed is effective, and the
technique to protect the antigen can be applied to other
antigens or proteins for oral delivery producing an
economical pathway for mass vaccination of fish.Graduation date: 1991
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Piganelli, Jon D. "Development of enteric protected vaccines for aquaculture /." 1994. http://hdl.handle.net/1957/8488.
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