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Development of candidate vaccine strategies against Rift Valley fever virus

Bhardwaj, Nitin (2011) Development of candidate vaccine strategies against Rift Valley fever virus. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    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.


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    Item Type: University of Pittsburgh ETD
    Creators/Authors:
    CreatorsEmailORCID
    Bhardwaj, Nitindrnitin.bhardwaj@gmail.com
    ETD Committee:
    ETD Committee TypeCommittee MemberEmailORCID
    Committee ChairRoss, Ted M.tmr15@pitt.edu
    Committee MemberKinchington, Paul R.kinchingtonp@upmc.edu
    Committee MemberReinhart, Todd A.reinhar@pitt.edu
    Committee MemberAyyavoo, Velpandivelpandi@pitt.edu
    Title: Development of candidate vaccine strategies against Rift Valley fever virus
    Status: Unpublished
    Abstract: 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.
    Date: 29 June 2011
    Date Type: Completion
    Defense Date: 26 January 2011
    Approval Date: 29 June 2011
    Submission Date: 02 March 2011
    Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
    Patent pending: No
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    URN: etd-03022011-144241
    Uncontrolled Keywords: Bunyavirus; DNA; Replicon
    Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
    Date Deposited: 10 Nov 2011 14:31
    Last Modified: 24 Feb 2012 11:27
    Other ID: http://etd.library.pitt.edu/ETD/available/etd-03022011-144241/, etd-03022011-144241

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