“I chose to pursue my graduate studies with the department of microbiology and immunology because the department demonstrated superior organization, which was evident as early as interview arrangements.  The faculty members are approachable, available to help, and are clearly committed to the growth of the students.  The department houses a wide variety of research endeavors; therefore every applicant can find a lab that meets his or her individual interests.  Additionally, from interactions with the current graduate students, I saw that they were happier in their studies and had a generally higher quality of life than what I observed at other schools.”

Research Project

Variola virus, the causative agent of smallpox, was eradicated by a global vaccination effort in 1980.  Due to decreased threat of exposure and the risk of complications from the live attenuated vaccine, routine immunization of the general population ceased in 1972.  These events have left a large portion of the US population naïve, and the remainder with unknown levels of protection.  The potential use of variola virus as a bioweapon has resulted in renewed efforts to develop a safe acellular vaccine against smallpox.   In view of its high potency as an adjuvant, flagellin is an outstanding candidate for use in a recombinant protein vaccine for this pathogen.  Such a vaccine would be safer than scarification with vaccinia virus and others cannot be infected through contact with an immunized individual. 

Prior work by other groups has established that complete protection against vaccinia virus challenge in mice can be achieved using three viral proteins, L1R, B5R, and A33R.  We have prepared purified recombinant forms of these proteins using a baculovirus expression system. In preliminary studies, we have evaluated the efficacy of flagellin in relationship to alum, the only adjuvant approved for use in humans.  Administration of the recombinant poxvirus proteins adsorbed on alum conferred 90% protection in response to lethal intranasal challenge with vaccinia virus and yielded L1R and B5R serum IgG titers of 380,000 and 480,000.  Immunization of pox proteins with alum and flagellin yielded L1R titers of 2 million and B5R titers of 1.6 million and conferred 100% protection to mice challenged with vaccinia virus.  Additionally, mice which were immunized with the recombinant pox proteins with alum and flagellin showed a decreased level of morbidity than those who received poxvirus proteins with alum only.  These results suggest that flagellin is a potent activator of humoral immunity and will require fewer boosts than a vaccine using alum alone.  Future studies will identify the virus-specific humoral and cell-mediated elements responsible for protection in this flagellin-based vaccine.