|
" Development of Adenovirus Vaccines to Combat Emerging Pathogens "
Anguiano-Zarate, Stephanie S.
Barry, Michael A.
| Document Type
|
:
|
Latin Dissertation
|
| Language of Document
|
:
|
English
|
| Record Number
|
:
|
1051871
|
| Doc. No
|
:
|
TL50988
|
| Main Entry
|
:
|
Anguiano-Zarate, Stephanie S.
|
| Title & Author
|
:
|
Development of Adenovirus Vaccines to Combat Emerging Pathogens\ Anguiano-Zarate, Stephanie S.Barry, Michael A.
|
| College
|
:
|
College of Medicine - Mayo Clinic
|
| Date
|
:
|
2019
|
| Degree
|
:
|
Ph.D.
|
| student score
|
:
|
2019
|
| Note
|
:
|
271 p.
|
| Abstract
|
:
|
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.
|
| Descriptor
|
:
|
Microbiology
|
|
|
:
|
Translation studies
|
|
|
:
|
Virology
|
| Added Entry
|
:
|
Barry, Michael A.
|
| Added Entry
|
:
|
College of Medicine - Mayo Clinic
|
| |