Rift Valley Fever virus (RVFV) is an arthropod-borne bunyavirus that causes a zoonotic disease associated with abortion storms, neonatal mortality in livestock and hemorrhagic fever with a high case/fatality ratio in humans. To date, vaccine developments against RVF have been based on inactivated or attenuated strains but their widespread use has been hampered due to deleterious effects or incomplete protection, justifying further studies to improve the existing vaccines or to develop others. To address this, DNA plasmid and alphavirus replicon vector (VEEV) expressing RVFV Gn glycoprotein were constructed and evaluated for their ability to induce protective immune responses in mice against RVFV. An experimental live-attenuated vaccine (MP12) and its inactivated counterpart (WIV MP12) were developed to serve as benchmarks for comparison. Test vaccine candidates efficiently expressed the RVFV glycoprotein in vitro and elicited anti-RVFV antibody responses in immunized mice, as determined by RVFV specific ELISA, IgG isotype ELISA, and virus neutralization. Interestingly, these vaccine strategies elicited cellular immune responses as determined by Gn specific ELISPOT. More importantly these vaccines not only protected immunized mice from virulent RVFV when challenged via intraperitoneal route, but also conferred protection when challenged via aerosol route. This work is of public health significance as it describes the development of safe and effective vaccine candidates that have the ability to protect both livestock and humans against possible routes of exposure to this zoonotic threat.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03022011-144241 |
| Date | 29 June 2011 |
| Creators | Bhardwaj, Nitin |
| Contributors | Paul R. Kinchington, Todd A. Reinhart, Ted M. Ross, Velpandi Ayyavoo |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03022011-144241/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0139 seconds