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      • HARVEST
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      • Graduate Theses and Dissertations
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      • HARVEST
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      Delivery of polynucleotides and oligonucleotides for improving immune responses to vaccines

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      PhDThesisBabiuk.pdf (3.105Mb)
      Date
      2003-04-03
      Author
      Babiuk, Shawn
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
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      Abstract
      Vaccination 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.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Pharmacy
      Program
      Pharmacy
      Committee
      Talbot, B.; Remillard, Alfred J. (Fred); Nazarali, Adil J.; Middleton, Dorothy M.; Foldvari, Marianna; Ellis, John A.; Baca-Estrada, Maria E.; van Drunen Littel-van den Hurk, Sylvia
      Copyright Date
      April 2003
      URI
      http://hdl.handle.net/10388/etd-04282003-084316
      Subject
      liposomes
      electroporation
      topical
      DNA vaccines
      CpG
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      • Graduate Theses and Dissertations
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