Date of Award
Master of Science (MS)
Microbiology and Immunology
Staphylococcus aureus is a gram-positive, extracellular bacterium that has emerged as an
important human pathogen. This bacterium is a leading cause of skin and soft tissue infections
(SSTIs) in humans, often leading to invasive and life-threatening infections. Treatment of S.
aureus infections is becoming more complicated due to the rise of methicillin-resistant S. aureus
(MRSA) strains, which are becoming increasingly resistant to a number of antibiotics. In the
United States, invasive MRSA infections result in more deaths annually than any other infectious
Despite a dire need, there is currently no vaccine against S. aureus infections. The failure
of past vaccine candidates may be due to a lack of understanding of immune correlates of
protection and how to obtain them through vaccination. Additionally, attempts to develop
vaccines have, up to this point, focused solely on eliciting high titer antibody responses to
antigens. Accumulating evidence from human patients and in vivo studies suggest that CD4+ T
cells are important mediators of protection from S. aureus infections.
TH17 cells, and their namesake cytokine IL-17, are involved in protection against
cutaneous infections. TH17 cells and IL-17 are important for neutrophil recruitment to sites of
infection, which is required for clearance of S. aureus, as well as antimicrobial peptide (AMP)
production from epithelial cells. Therefore, a protective vaccine will likely require a strong TH17
response to S. aureus antigen. Data also implicates TH1 cells and the associated cytokine IFN? as
important mediators of protection against S. aureus, especially during invasive infection. Based
on these data, the most effective vaccine will likely be one that can elicit strong TH17 and TH1
responses against vaccine antigens.
My goal was to develop an adenovirus (Ad) vector based vaccine that could provide
protection from cutaneous MRSA infections. Ad is an attractive vaccine vector due to its potent
T cell adjuvant capabilities and high level and duration of transgene expression. As T cells have
been shown to be important for immunity to S. aureus, I hypothesized that Ad vectors expressing
domains from MRSA surface proteins as transgenes would elicit more potent T cell responses to
these antigens than protein immunization and would provide protection from cutaneous
infection. I generated Ad vectors expressing MRSA antigens and assessed the immune response
induced by vaccination. I also assessed the ability of these Ad vectors to provide protection
against MRSA infection using a mouse model of cutaneous infection.
Orvis, Emily, "Immunobiology of Adenovirus-Vector Vaccines for MRSA" (2018). Master's Theses. 3752.
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Copyright © 2018 Emily Orvis