Dissertation Defense Announcement:
To: The George Mason University Community

Tony Pierson
PhD Biosciences Candidate

Date:   Thursday April 7, 2011
Time:   11:30 a.m. 
Place:  George Mason University
 	     Bull Run Hall, Room 249
	     Prince William campus
  
Dissertation Chair: Dr. Monique van Hoek
Committee members: Dr. Charles L. Bailey, Dr. Calvin Carpenter, Dr. Barney Bishop
Title: "Specific and Innate Immunity Against Francisella"

The dissertation is on reserve in the Johnson Center Library, Fairfax campus.The doctoral project will not be read at the meeting, but should be read in advance.

All members of the George Mason University community are invited to attend.

ABSTRACT:

Francisella tularensis is a highly infectious gram negative bacterium which causes tularemia.

Francisella produces outer membrane vesicles (OMVs), which release many proteins into the extracellular proteome. We successfully demonstrate that a novel Francisella OMV vaccine delivered intranasally protects BALB/C mice challenged with up to 100 LD50 of intranasally delivered Francisella. Next we demonstrate that mutations in the Tol/Pal system in Francisella results in OMV over-production. This finding may lead to a method of producing larger amounts of OMVs for future vaccine production. Next, we measured changes in transcription of well characterized as well as novel human β defensin (hBD) genes upon exposure to Francisella. We observed increased induction of transcription of hBDs when compared to the negative control. To demonstrate translation, we used ELISA and found that the amount of hBD protein in supernatant from each treatment group was significantly higher than the negative control. We also visualized hBD2 colocalized with Francisella. Together, these finding demonstrate that hBDs are stimulated by and associated with Francisella bacteria as well as their OMVs. Finally, we showed that hBDs stimulate the production of OMVs in vitro. Taken together, this research establishes that OMVs stimulate the innate as well as specific immunity in a manner similar to whole bacteria. However, OMVs are acellular, and as such represent a novel vaccine candidate which is capable of stimulating both innate and specific immunity.

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