عنوان

Development of Adenovirus Vaccines to Combat Emerging Pathogens

Number

TL50988

.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

Text of Note

271 p.

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.

Subject Term

Microbiology

Subject Term

Translation studies

Subject Term

Virology

Anguiano-Zarate, Stephanie S.

Barry, Michael A.

College of Medicine - Mayo Clinic

Electronic name

p

[Thesis]

276903

a

Y