The Development and Characterization of Computationally Optimized Broadly Reactive Antigen (Cobra) for H5NX Influenza Viruses
General Material Designation
[Thesis]
First Statement of Responsibility
Nunez, Ivette Ariela
Subsequent Statement of Responsibility
Ross, Ted M.
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
University of Georgia
Date of Publication, Distribution, etc.
2020
GENERAL NOTES
Text of Note
193 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
Ph.D.
Body granting the degree
University of Georgia
Text preceding or following the note
2020
SUMMARY OR ABSTRACT
Text of Note
Avian influenza viruses pose a constant threat to the human population and continuously circulate around the globe in wild water fowl species. Due to migratory patterns, these hosts commonly come into contact with susceptible species including domestic chicken, turkeys and ducks. Close contact with such species leaves poultry farmers and live-market patrons at risk for contracting this deadly disease. Current strategies to contains such spill-over events can become problematic, especially those concerning culling and have negative economic impacts. Multiple countries, including the United States, depend on the poultry industry as a main source of economical income. When avian influenza viruses spill over into the human population, the results are catastrophic, ultimately resulting in systemic infection and ultimately death. Vaccines currently stockpiled for such an outbreak are poorly immunogenic and are obsolete facing the rapidly changing antigenic nature of influenza viruses. Combating this problematic virus is centered around developing an avian influenza vaccine that is able to induce cross-reactive antibodies against multiple viral clades, is highly immunogenic, and involves a dose-sparing technique. The studies discussed in this body of work investigate the molecular epitopes responsible for antibody elicitation, design of new immunogenic vaccines, and explores the importance of pre-immune status on avian influenza virus infection. The importance of glycosylation of hemagglutinin based vaccines was explored through site-directed mutagenesis, and was thoroughly tested in a mouse pre-clinical model of disease. We demonstrated that glycosylation of the hemagglutinin determines immunogenicity and effectiveness of eliciting cross-reactive antibodies against multiple viral clades.