Viral vector-based vaccines represent an effective means of in vivo antigen expression and the ensuing generation of a sustained immune response in the host. These new generation vaccines are deemed promising against pathogens for which researchers have so far failed to put forth preventive strategies and/or effective, accessible, treatment modalities. HIV-1 stands at the foremost of this list. In the current study, we have evaluated the use of two different viral vector-based vaccines against Clade A of HIV-1, namely recombinant modified vesicular stomatitis virus (VSV-AV3) and Adenovirus serotype 5 (Ad5) expressing the Gag protein from subtype A. These viral vectors, which are also inherently endowed with adjuvant properties, were delivered via a mucosal immunization strategy in a humanized transgenic mouse model. Transgenic mice expressing both HLA-A*0201 and HLA-DR*0101 represent a versatile model in which HIV-specific immunogenic epitopes and the resulting T cell receptor (TCR) specificity can be determined. We show that following mucosal delivery of vaccine, there is induction of antigen-specific systemic T cells against epitopes which were previously shown to be immunogenic in humans. We next developed novel multimeric reagents for the detection of CD4 + T cells, namely dodecameric HLA-DR1 molecules using a murine immunoglobulin M (IgM) scaffold. These reagents aim at increasing the overall avidity of peptide-MHC Class II complexes to detect low-affinity TCRs. These multimers were able to activate in vitro a Jurkat T cell line in an antigen-specific manner. The identification and characterization of the molecular requirements boosting the qualitative and quantitative features of the immune response to HIV vaccines, in addition to the development of novel state-of-the-art immune monitoring tools, will be crucial in better understanding of the mechanisms of interaction between the virus and the host immune system, leading to rational strategies in the fight against the AIDS epidemic.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.103163 |
| Date | January 2006 |
| Creators | Kalfayan, Lina H. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Microbiology and Immunology.) |
| Rights | © Lina H. Kalfayan, 2006 |
| Relation | alephsysno: 002584918, proquestno: AAINR32359, Theses scanned by UMI/ProQuest. |
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