عنوان

Development of Adenovirus Vaccines to Combat Emerging Pathogens

Number

TLpq2284673757

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Development of Adenovirus Vaccines to Combat Emerging Pathogens

General Material Designation

[Thesis]

First Statement of Responsibility

Anguiano-Zarate, Stephanie S.

Subsequent Statement of Responsibility

Barry, Michael A.

Name of Publisher, Distributor, etc.

College of Medicine - Mayo Clinic

Date of Publication, Distribution, etc.

2019

Specific Material Designation and Extent of Item

271

Dissertation or thesis details and type of degree

Ph.D.

Body granting the degree

College of Medicine - Mayo Clinic

Text preceding or following the note

2019

Text of Note

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.

Microbiology

Translation studies

Virology

Anguiano-Zarate, Stephanie S.

Barry, Michael A.

Electronic name

p

[Thesis]

276903

a

Y