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" Development of Adenovirus Vaccines to Combat Emerging Pathogens "
Anguiano-Zarate, Stephanie S.
Barry, Michael A.
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1104980
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| Doc. No
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TLpq2284673757
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| Main Entry
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Anguiano-Zarate, Stephanie S.
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Barry, Michael A.
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| Title & Author
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Development of Adenovirus Vaccines to Combat Emerging Pathogens\ Anguiano-Zarate, Stephanie S.Barry, Michael A.
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| College
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College of Medicine - Mayo Clinic
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| Date
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2019
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| student score
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2019
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| Degree
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Ph.D.
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| Page No
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271
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| Abstract
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Today, infectious diseases are only a plane ride away. With the rise in vaccine-preventable diseases and the development of multidrug resistant organisms, the World Health Organization has issued a 5-year plan to address these public health threats. The overall goal of this thesis was to generate adenovirus-based (Ad) vaccines against the emerging viral pathogen Ebola and the bacterial pathogen Staphylococcus aureus (S. aureus). In the first application, we engineered a single-cycle Ad6 expressing the Ebola glycoprotein (SC-Ad6-EBOV GP) that, when used as a muscular and mucosal intranasal immunization, generated antigen-specific binding antibodies in mice, hamsters, and rhesus macaques. These responses neutralized luciferase expression derived from a recombinant-vesicular stomatitis virus (rVSV-EBOV Luc) used as a pseudo-challenge virus in mice and hamsters. When comparing Ad and rVSV, both vaccines elicited pH stable serum antibodies that were strongest in animals receiving a heterologous prime-boost. These data suggest that SC-Ad6-EBOV GP may be useful during future EBOV outbreaks. In the second application, we engineered and tested a set of Ad vaccines expressing select target antigens involved in important S. aureus infection processes. This thesis also briefly investigates the use of Syrian hamsters as a novel model for S. aureus infection. Importantly, our replication-defective Ad5 vaccine that expresses an inactive mutant form of the alpha-hemolysin (RD-Ad5-Hla) generated neutralizing antibodies that protected against lethal toxin challenge for longer than a year after a single immunization in mice. Lastly, we placed the generation of novel immunizations in the context of the current vaccine climate. Altogether, these data suggest that utilizing gene-based Ad vaccines may be useful in targeting key antigens for the emerging pathogens Ebola and S. aureus.
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Microbiology
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Translation studies
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Virology
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