Development of Adenovirus Vaccines to Combat Emerging Pathogens
نام عام مواد
[Thesis]
نام نخستين پديدآور
Anguiano-Zarate, Stephanie S.
نام ساير پديدآوران
Barry, Michael A.
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
College of Medicine - Mayo Clinic
تاریخ نشرو بخش و غیره
2019
مشخصات ظاهری
نام خاص و کميت اثر
271
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
College of Medicine - Mayo Clinic
امتياز متن
2019
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
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.
موضوع (اسم عام یاعبارت اسمی عام)
موضوع مستند نشده
Microbiology
موضوع مستند نشده
Translation studies
موضوع مستند نشده
Virology
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )