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Dissertation - University Access Only
Doctor of Philosophy (PhD)
Veterinary and Biomedical Sciences
Rift Valley Fever virus is a high-consequence, infectious, zoonotic disease endemic in Africa, and a constant threat to US Agriculture. A chimeric virus-like particle (VLP)- based RVFV vaccine demonstrated rapid onset of immunity with high antibody titers to the N protein after a single injection, whereas two doses generated virus-neutralizing antibodies that were three times higher than the one-dose administration. A subunit vaccine based on RVFV glycoproteins Gn and Gc elicited high titers after a two-dose regimen, including both ELISA-reactive (up to 1:6400) and virus neutralizing antibodies (1:1280). The highest titers were generated with the use of the adjuvant Montanide ISA 206 VG, alone or in combination with inulin acetate microparticles. The RVFV Gn peptides immunological responses were determined. One of these peptides was particularly effective as a B cell antigen, whereas the other two appeared to promote T cell responses. In follow up studies, T-cell lines specific to the RVFV Gn glycoprotein were generated by stimulation of PBMC from RVFV Gn-immunized animals. In response to one of the peptides CD4+ T cell line was generated. Activation with the other two peptides gave both CD4+ and CD8+ Gn-specific T cells. In a final series of experiments, a novel population of myeloid-like γδ T cells and their role in RVFV vaccination was defined. In vivo sheep studies showed rapid (in the first 4 days) expansion of this CD11b+ subset of γδ T cells in response to vaccine xiv adjuvant, prior to an overall increase of γδ T cells. In vitro culture studies displayed an increased frequency of non-proliferating CD11b+, CD14, CD86, CD40, MHCII+ subset of γδ T cells during culture in the absence of exogenous mitogen. These cells also produced IFNγ and were able to process antigens, presumably for MHC-mediated presentation. Together, these results demonstrate the development of both B and T cell responses to RVFV subunit vaccines, and provide new avenues to characterize the antibody and cellular response in vitro. In addition, we have defined a population of -T cells with apparently significant roles in the initiation of the immune response in sheep.
Library of Congress Subject Headings
Rift Valley fever -- Vaccination
Includes bibliographical references (pages 127-143)
Number of Pages
South Dakota State University
In Copyright - Educational Use Permitted
Lebedev, Maxim, "Immune Response to Rift Valley Fever Virus Vaccines and Development of Tools for its Elevation" (2015). Electronic Theses and Dissertations. 1815.