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Please use this identifier to cite or link to this item: http://hdl.handle.net/1993/5069

Title: The creation of a hantavirus vaccine using reverse genetics and its evaluation in the lethal Syrian hamster model
Authors: Brown, Kyle
Supervisor: Feldmann, Heinz (Medical Microbiology)
Examining Committee: Coombs, Kevin (Medical Microbiology) Pind, Steven (Biochemistry and Medical Genetics) Panganiban, Antonito (University of New Mexico)
Graduation Date: February 2012
Keywords: Vaccine
Hantavirus
Issue Date: 1-Dec-2011
Publisher: American Society for Microbiology
Citation: Brown, K. S., D. Safronetz, A. Marzi, H. Ebihara, and H. Feldmann. 2011. Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes Virus. J Virol 85:12781-12791.
Abstract: Andes virus (ANDV) is a highly pathogenic New World hantavirus found in Chile and Argentina that causes Hantavirus Pulmonary Syndrome (HPS). A significantly high case fatality rate, the potential for human-to-human transmission, and the lack of licensed vaccines or effective treatments for the disease suggest an urgent need for the development of such measures. Many vaccine platforms have been recently described using reverse genetics systems to generate attenuated virus strains, as well as recombinant viruses expressing foreign proteins. This study attempted to generate and characterize vaccines based on an ANDV infectious clone system, as well as a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV glycoprotein precursor (VSVΔG/ANDVGPC), to test their efficacy in the only lethal disease animal model of HPS. Although an ANDV infectious clone system was not successfully established, precluding its use as a possible vaccine candidate, the first New World hantavirus minigenome system was described. In addition, Syrian hamsters immunized with a single dose of the recombinant VSVΔG/ANDVGPC vaccine were fully protected against disease when challenged at 28, 14, 7, or 3 days post-immunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ, depending on the time point of immunization. At 28 days post-immunization, a lack of detectable ANDV RNA in tissue samples as well as a lack of seroconversion against the ANDV nucleoprotein (N) in nearly all hamsters suggested mostly sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV GN/GC antibodies that seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 and 3 days before challenge also resulted in full protection, but the lack of a neutralizing humoral immune response and the up-regulation of hamster cytokines involved in innate pathways suggested a possible role of innate responses in protection. The role of innate immunity was supported by the fact that administration of the vaccine 24 hours post-challenge was successful in protecting 90% of hamsters. Overall, the data suggests the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/post-exposure treatment against lethal hantavirus infections.
URI: http://hdl.handle.net/1993/5069
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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