Dissertations / Theses: 'DNA vaccines'

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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3

Bandholtz, Lisa Charlotta. "DNA vaccines and bacterial DNA in immunity /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-340-6/.

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4

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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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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6

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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7

Roos, Anna-Karin. "Delivery of DNA vaccines against cancer /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-895-9/.

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8

Triyatni, Miriam. "Studies on the protective and therapeutic efficacy of duck hepatitis B virus vaccines /." Title page, table of contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09pht842.pdf.

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Thesis (Ph. D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999.
Copies of author's previously published article inserted onto back cover. Includes bibliographical references (leaves 164-187).

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9

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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10

Hobson, Philip Stanley. "Optimising the efficacy of plasmid DNA vaccines." Thesis, King's College London (University of London), 2004. https://kclpure.kcl.ac.uk/portal/en/theses/optimising-the-efficacy-of-plasmid-dna-vaccines(fd48c033-ff46-4c9b-b3cb-dc63c02c7824).html.

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11

Obrenovic, Milka. "Niosomes as delivery system for DNA vaccines." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271467.

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12

Gabler, Maximilian. "DNA Replicons next generation vaccines against allergy." Saarbrücken VDM Verlag Dr. Müller, 2005. http://d-nb.info/988936151/04.

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13

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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Atuah, Kwame N. "Development of plasmid dna formulations for application as microspheric dna vaccines." Thesis, Aston University, 2001. http://publications.aston.ac.uk/10942/.

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This thesis describes an investigation into the fabrication of plasmid DNA, the active principle of DNA vaccines, into microspheres, based on the tenet of an increased cellular uptake of microparticulate matter by phagocytic cells. The formulation of plasmid DNA into microspheres using two methods, is presented. Formulation of microspheric plasmid DNA using the double emulsion solvent evaporation method and a spray-drying method was explored. The former approach involves formation of a double emulsion, by homogenisation. This method produced microspheres of uniform size and smooth morphology, but had a detrimental effect on the formulated DNA. The spray-drying method resulted in microspheres with an improved preservation of DNA stability. The use of polyethylenimine (PEI) and stearylamine (SA) as agents in the microspheric formulation of plasmid DNA is a novel approach to DNA vaccine design. Using these molecules as model positively-charged agents, their influence on the characteristics of the microspheric formulations was investigated. PEI improved the entrapment efficiency of the plasmid DNA in microspheres, and has minimal effect on either the surface charge, morphology or size distribution of the formulations. Stearylamine effected an increase in the entrapment efficiency and stability of the plasmid DNA and its effect on the micropshere morphology was dependent on the method of preparation. The differences in the effects of the two molecules on microsphere formulations may be attributable to their dissimilar physico-chemical properties. PEI is water-soluble and highly-branched, while SA is hydrophobic and amphipathic. The positive charge of both molecules is imparted by amine functional groups. Preliminary data on the in vivo application of formulated DNA vaccine, using hepatitis B plasmid, showed superior humoral responses to the formulated antigen, compared with free (unformulated) antigen.

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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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Molloy, Sally Dixon. "A DNA Vaccine Against Infectious Pancreatic Necrosis Virus." Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/MolloySD2007.pdf.

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17

Kjerrström, Zuber Anne. "Enhancement of HIV-1 DNA immunogens /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-304-x.

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18

Tse, Man Tsuey. "Development of microparticulate DNA vaccines for pulmonary delivery." Thesis, University College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.483701.

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19

Yang, Jyh-Chyang. "Liposome-based subunit and DNA hepatitis B vaccines." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367733.

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20

Forconi, Francesco. "Development of DNA vaccines against B-cell neoplasms." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396194.

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21

Watkins, Jane Katharyn. "Inducing immunity to haematological malignancies with DNA vaccines." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418048.

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22

Haygreen, Elizabeth Ann. "Enhancing in ovo vaccination using novel DNA vaccines." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407821.

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23

Lee, Delphine Juihoa. ""Naked" plasmid DNA vaccines : cellular roles and applications /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1999. http://wwwlib.umi.com/cr/ucsd/fullcit?p9944207.

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24

Cheung, Ying Kit. "Study of the immunity of a human papillomavirus vaccine candidate /." View Abstract or Full-Text, 2003. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202003%20CHEUNG.

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Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003.
Includes bibliographical references (leaves 112-129). Also available in electronic version. Access restricted to campus users.

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25

Rollman, Erik. "Concepts in DNA immunization : overcoming viral diversity and enhancing plasmid immunogenicity /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-943-9/.

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Hatfield, Rachel Sarah. "Development of a polymeric delivery system for DNA vaccines." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299706.

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27

Li, Wenqin. "Novel intranasal GNRs-DNA vaccines against human papillomavirus infection." Thesis, University of Strathclyde, 2015. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=28807.

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Wilson, Erica Barbara. "Development of novel DNA based vaccines for cancer immunotherapy." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615721.

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29

Ruiz, Elena. "DNA fusion vaccines against HPV16 E7 antigen-associated cancers." Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/374745/.

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To date, the success of cancer vaccines in human clinical trials has been limited. One of the reasons for this is the immunological tolerance to tumour antigens found in cancer patients. A novel DNA fusion vaccine design which links a pathogen-derived domain (DOM) of fragment C from tetanus toxin to a peptide epitope from a tumour antigen has been developed in our laboratory. The microbial sequence is able to activate a non-tolerised pool of helper T cells, providing T-cell help for immune induction against the linked tumour-specific sequence. The main aim of this project was to produce a therapeutic DNA vaccine against human papillomavirus (HPV)-associated cancers. A number of DNA fusion vaccines against the E7 antigen from HPV16 were constructed, including pDOM.E749-57, which encodes a well described H-2Db-binding epitope from E7 fused to the DOM sequence. CD8+ T-cell responses to the vaccines were demonstrated using flow cytometry and functional assays. Importantly, these responses were stronger than those induced by a published synthetic long peptide strategy. In vivo tumour challenge experiments showed that DNA vaccines had a protective and therapeutic effect. The vaccines were then tested in transgenic mice which develop spontaneous E7-expressing tumours in a setting of tolerance. DNA vaccine-mediated E7-specific CD8 + T-cell responses were successfully induced in these mice, together with a reduction in the mass of spontaneous tumours. This is the first demonstration of pDOM-epitope DNA vaccine-mediated therapy for spontaneous tumours and bodes well for translation into the clinic. One limiting factor for DNA vaccination in humans may be the delivery system. Electroporation (EP) is one approach which may overcome this. Therefore, a secondary aim of this project was to investigate the impact of EP on immune responses to DNA vaccination in more detail. EP proved essential for generating T-cell and antibody responses to the pDOM.E7 49-57 vaccine in sub-optimal conditions. This information will be crucial for the planning of therapeutic vaccination protocols in patients.

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Benvenuti, Federica. "DNA vaccines for the immunotherapy of B-cell lymphoma." Doctoral thesis, SISSA, 2000. http://hdl.handle.net/20.500.11767/4742.

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Working at the International Centre for Genetic Engeneering and Biotechnology, where I started my Ph.D thesis in October '96 I have directed my research activity to the immunotherapy of B-cell malignancies by DNA vaccination. I have developed an efficent vaccination strategy to induce protection in the BCL1 lynphoma model and characterized all the elements of the antigen encoding plasmid that contribute to the induction of the immune response. In addition, I have investigated the structural requirements of the idiotypic/anti-Idiotypic interaction following scFv DNA vaccination. Thuis analysis revealed that the polyclonal anti-Id immune response induced by scFv DNA vaccination is exclusively directed against conformational combined epitopes. Remarkably, the same immunogen delivered in a different form induced also antibodies directed against chain specific determinants suggesting that the mode of presentation to the immune system may influence the specifity of the antibody response.

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Gaucher, Denis. "DNA vaccination against Entamoeba histolytica." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82877.

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Invasive amebiasis, caused by the protozoan parasite Entamoeba histolytica, is one of the leading parasitic causes of mortality worldwide, and there are no vaccines available to control the disease. The heavy subunit of the E. histolytica Gal-lectin is regarded as a potential subunit vaccine candidate. A Th1 (cell-mediated) immune response is protective against invasive amebiasis, and DNA vaccination is a strategy to induce such a response against specific antigens. The objective of this study was to construct and test a Gal-lectin-based DNA vaccine against E. histolytica. DNA encoding as 894--1081 of the Gal-lectin heavy subunit was resynthesized using a gerbil codon frequency bias and inserted in a mammalian expression vector to generate the DNA vaccine pCISToGL6. Balb/c mice vaccinated intradermally developed a Gal-lectin-specific cellular immune response, as well as an anti-Gal-lectin humoral immune response. Serum antibodies recognized a recombinant portion of the Gal-lectin heavy subunit by immunoblot and ELISA, and bound to native Gal-lectin on the surface of live trophozoites, inhibiting adherence to target cells. The Gal-lectin-specific serum antibodies were of the IgG2a isotype, indicating that a Th1 response was stimulated by the vaccine. We were also interested in using DNA encoding IL-12, IL-18 or GM-CSF as genetic adjuvants co-injected with pCISToGL6 to potentiate the immune response. Since the DNA vaccine was destined to confer protection in the gerbil model of invasive amebiasis, we cloned gerbil IL-12 (p35 and p40), IL-18 and its convertase caspase-1, and GM-CSF. The proteins were expressed in mammalian cells and showed bioactivity in vitro. Taken together, these results have laid the foundation to optimize and test a working Gal-lectin with co-stimulatory molecules to elicit a Th1 immune response for protective immunity against invasive amebiasis.

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32

Pavlenko, Maxim. "Induction of T-cell responses against PSA by plasmid DNA immunization /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-385-X/.

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33

Law, Man-sun. "DNA vaccine against chicken infectious bursal disease virus /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20128393.

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Ljungberg, Karl. "Variable viral genes as genetic immunogens /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-399-6/.

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Allsop, Julie Kay. "Development of nucleic acid vaccines for mucosal delivery." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263104.

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Meynell, Helen Mary. "Bacterial modulation of particle transport across the follicle-associated epithelium of Peyer's patches." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285656.

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37

Halladay, Jeff. "Chitosan nanoparticles for mucosal and intramuscular delivery of DNA vaccines." Thesis, Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/17267.

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38

Johansson, Elin. "Effects of immunostimulatory DNA in the pig : induction of immunoregulatory cytokines by plasmid DNA, virus or bacteria /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 2002. http://epsilon.slu.se/avh/2002/91-576-5949-4.pdf.

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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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Aasa, Chapman Marlen Maria Isabell. "Investigation of DNA vaccines against Coxsackie virus 3 induced myocarditis." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248448.

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Li, Xiong Wei. "Development of new DNA vaccines utilising polymeric gene delivery system." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427931.

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Kotecha, Minal Tarunkant. "DNA vaccines : a development of novel strategies for tumour prevention." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408716.

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McNicholl, Feargal Patrick. "Development of DNA vaccines for patients following stem cell transplantation." Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432035.

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Robertson, James Stuart. "DNA and protein based vaccines against Salmonella enterica Serovar Typhimurium." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/14307.

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GroEL is a heat shock protein, involved in the folding of denatured proteins under stressed conditions. Flagellin is a structured protein of flagella, and can undergo phase variation so that at any one time, synthesis of flagellin occurs from either of two genes, fliC or fliB. Porins, of which OmpC is an example, allow passage of nutrients and small molecules through the bacterial cell outer membrane. All of these proteins have previously been described as being immunogenic. In the work described here, antibodies specific to each of these antigens were detected in both innately susceptible and resistant mice after infection with an attenuated strain of S. typhimurium, and after subsequent challenge with the virulent organism, suggesting that they may each be involved in protective immunity. The immunogenicity of a vaccine consisting of these four recombinant Salmonella antigens was assessed in the mouse model. GroEL- and flagellin-specific antibodies were detected in innately susceptible mice after immunisation together with the adjuvant DDA. Moreover, analysis of IgG isotypes showed increased titres of both IgG1 and IgG2a, the latter indicating that cell-mediated immunity had been generated. However, challenge of immunised mice with virulent S. typhimurium demonstrated that the protective efficacy of the vaccine was of only low-level. Immunisation of innately susceptible and resistant mice using a tetravalent DNA vaccine expressing all four antigens resulted in increased antibody against GroEL, FliC and FlijB in both mouse strains. As with the subunit vaccine, IgG isotype analysis showed increased titres of both IgG1 and IgG2 indicting that both Type 2 and Type 1 helper T-cell responses had been elicited. However, considerable variation was observed within immunised mouse groups and so the protective efficacy of the vaccine was not determined.

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Gomez, Clarissa Sara. "In-vivo delivery of DNA vaccines using metallo-lipid nanoparticles." To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2008. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.

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McCormick, Adele. "Enhancement of the immunogenicity of recombinant gp120 of HIV-1." Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366115.

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King, Catherine Anne. "Idiotypic vaccination against B cell tumours." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241861.

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Wells, Andrew. "Development and evaluation of biodegradable carriers for nucleic acid vaccines." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311757.

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Bruffaerts, Nicolas. "Preclinical studies on a new strategy combining the Bacillus of Calmette-Guérin with plasmid DNA-based subunit vaccines against tuberculosis." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209082.

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La tuberculose est une maladie contagieuse causée par les bactéries appartenant au complexe Mycobacterium tuberculosis. On estime près de neuf millions de nouveaux cas et un million de décès chaque année dans le monde. De plus, approximativement un tiers de la population mondiale est infecté de manière latente, donc à risque de développer la maladie. Le seul vaccin préventif jusqu’à présent disponible est le Bacille de Calmette-Guérin (BCG). Cependant, son efficacité contre la forme pulmonaire de la maladie, contagieuse et plus fréquente chez l’adulte, est extrêmement variable. Le développement de nouveaux vaccins prophylactiques contre la tuberculose est basé sur une stratégie de remplacement ou d’amélioration de l’actuel vaccin BCG. De nombreux candidats vaccins sous-unitaires sont évalués dans un protocole de vaccination de rappel après le BCG. Ce dernier est en effet administré à plus de 80% des nouveau-nés et des nourrissons des populations à haut risque.

Le présent travail a eu pour but principal d’étudier une nouvelle approche de vaccination combinant le Bacille de Calmette-Guérin avec des vaccins sous-unitaires à ADN plasmidique dans différents modèles précliniques.

Plusieurs hypothèses tentent d’expliquer la faible efficacité du vaccin BCG, comme la faible induction de réponses immunitaires de type cellulaire T CD8+, le déclin de l’immunité protectrice induite au cours du temps, ou son répertoire antigénique limité. Les vaccins à ADN plasmidique induisant de telles réponses, le travail proposé a consisté au développement d’un nouveau protocole de vaccination basé sur la coadministration par la voie intradermique du vaccin BCG formulé avec un vaccin à ADN plasmidique codant pour un antigène mycobactérien. Nous avons observé dans plusieurs modèles murins (adulte et néonatal) une augmentation significative des réponses cellulaires de type CD4+ Th1 et CD8+, ainsi que de la réponse humorale spécifique. L’immunogénicité de cette approche a également été analysée dans un modèle animal de grande taille, à savoir le modèle porcin. Les résultats obtenus indiquent que les vaccins à ADN plasmidique sont capables d’augmenter les réponses spécifiques à l’antigène codé par le plasmide mais également celles spécifiques à d’autres antigènes exprimés par le vaccin BCG. Enfin, dans la deuxième partie du travail, nous avons développé des vaccins plasmidiques codant pour des combinaisons d’antigènes phase-spécifiques de M. tuberculosis et nous avons analysé leur immunogénicité en modèle murin.

En conclusion, nous avons montré que la stratégie de coadministration par la voie intradermique du vaccin BCG avec un vaccin à ADN plasmidique encodant des antigènes mycobactériens s’avère être un protocole de vaccination réaliste et efficace pour améliorer l’immunité induite par le vaccin BCG. Elle offre par ailleurs des perspectives pour être appliquée avec des plasmides codant pour des antigènes caractéristiques de la tuberculose latente, peu reconnus après vaccination BCG, pour protéger à la fois contre la tuberculose active d’une primo-infection et contre la réactivation d’une infection latente.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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Vittes, Gisella E. "Developing DNA Vaccines against the Cancer-Related Prostate-Specific Membrane Antigen." Thesis, University of Southampton, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509466.

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Dissertations / Theses on the topic 'DNA vaccines'

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