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Document Type

Dissertation - University Access Only

Award Date

2015

Degree Name

Doctor of Philosophy (PhD)

Department / School

Veterinary and Biomedical Sciences

First Advisor

Alan Young

Abstract

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
Immune response
Sheep--Immunology.

Description

Includes bibliographical references (pages 127-143)

Format

application/pdf

Number of Pages

157

Publisher

South Dakota State University

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Rights Statement

In Copyright