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Delivery of polynucleotides and oligonucleotides for improving immune responses to vaccines

dc.contributor.committeeMemberTalbot, B.en_US
dc.contributor.committeeMemberRemillard, Alfred J. (Fred)en_US
dc.contributor.committeeMemberNazarali, Adil J.en_US
dc.contributor.committeeMemberMiddleton, Dorothy M.en_US
dc.contributor.committeeMemberFoldvari, Mariannaen_US
dc.contributor.committeeMemberEllis, John A.en_US
dc.contributor.committeeMemberBaca-Estrada, Maria E.en_US
dc.contributor.committeeMembervan Drunen Littel-van den Hurk, Sylviaen_US
dc.creatorBabiuk, Shawnen_US
dc.date.accessioned2003-04-28T08:43:16Zen_US
dc.date.accessioned2013-01-04T04:30:03Z
dc.date.available2004-04-28T08:00:00Zen_US
dc.date.available2013-01-04T04:30:03Z
dc.date.created2003-04en_US
dc.date.issued2003-04-03en_US
dc.date.submittedApril 2003en_US
dc.description.abstractVaccination is one of the major achievements of modern medicine. As a result of vaccination, diseases such as polio and measles have been controlled and small pox has been eliminated. However, despite these successes there are still many diseases of microbial origin that cause tremendous suffering because there are no vaccines or the vaccines available are inadequate. The development of DNA based vaccines and immunostimulatory CpG oligonucleotides (ODNs) as adjuvants offer new possibilities for developing new vaccines. The objectives of this research were to improve the delivery of polynucleotides and oligonucleotides to enhance their potency and to evaluate the feasibility of non-invasive methods for the delivery of vaccines through the skin in order to improve the safety and the ease of administration of human and veterinary vaccines. The results demonstrated that topical administration of plasmids in a lipid-based delivery system (biphasic lipid vesicles [Biphasix™]) resulted in gene expression in the draining lymph nodes, as well as induction of antigen specific immune responses in mice. The use of electroporation significantly enhanced both gene expression and immune responses to DNA vaccines in pigs. Prior treatment with electroporation enhanced immune responses to both protein and DNA vaccines indicating that both gene expression and tissue damage are important mechanisms that electroporation uses to enhance immune responses. In addition, the formulation of CpG ODNs in biphasic lipid vesicles (BiphasixTM) called Vaccine-Targeting Adjuvant (VTA) enhanced immune response to protein antigens following systemic and mucosal administration.en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-04282003-084316en_US
dc.language.isoen_USen_US
dc.subjectliposomesen_US
dc.subjectelectroporationen_US
dc.subjecttopicalen_US
dc.subjectDNA vaccinesen_US
dc.subjectCpGen_US
dc.titleDelivery of polynucleotides and oligonucleotides for improving immune responses to vaccinesen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentPharmacyen_US
thesis.degree.disciplinePharmacyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US

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