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Title page for ETD etd-0107102-160706


Document Typethesis
Author NameFarfan Arribas, Diego Jose
URNetd-0107102-160706
TitleDNA Vaccines Against HIV-1: Augmenting Immunogenicity of gp120
DegreeMS
DepartmentBiology & Biotechnology
Advisors
  • David S. Adams, PhD, Advisor
  • Shan Lu, MD, PhD, Co-Advisor
  • Joseph C. Bagshaw, Committee Member
  • Keywords
  • Gene Therapy
  • Immunology
  • Vaccine
  • HIV
  • AIDS
  • Date of Presentation/Defense2002-01-07
    Availability unrestricted

    Abstract

    There is currently no protective vaccine against HIV. It is known that a high mutation rate and the existence of many subspecies or clades generated by point mutations or recombination events, are at least partly responsible for the ability of the virus to escape immune responses elicited by classical vaccines. Protein subunit vaccines may not be effective due to this pronounced viral mutability. An immune evasion mechanism has been postulated in which variable domains occlude conserved epitopes crucial for infectivity. The use of DNA vaccines appeared as a favorable approach. Here, a DNA vaccine approach is presented in which the DNA constructs have been engineered to circumvent the aforementioned problems by 1) introducing elements to enhance expression, such as a heterologous promoter, a heterologous signal sequence and intron sequences, 2) by optimizing codon usage, and 3) by vaccinating with antigens that have a modified glycosylation pattern which will make them more immunogenic.

    The results indicated that deglycosylation of different clades of gp120 did not affect the protein conformation, and ‘in vitro’ expression levels were good. Antigen codon optimization dramatically increased antibody production. In the animals vaccinated with non-codon-optimized constructs, the presence of an intron and a heterologous signal sequence was required to achieve a good antibody response. Therefore, antigen engineering is required to obtain a powerful immune response against HIV-1 gp120.

    Files
  • arribas.pdf

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