Biology Colloquium

Biology Colloquium

Postby cdouglas » Wed Dec 05, 2012 4:07 pm


Dr. Kasey Karen
Department of Molecular Microbiology and Immunology
School of Public Health
John Hopkins University

“Adenovirus: From Vaccine Vector
to Model System”

Wednesday, December 12, 2012
3:00-4:00 PM
Conley Arts Building, Room 101

Live adenovirus (Ad) delivered orally to the gastrointestinal tract has been used as a vaccine against adenovirus-induced respiratory illness for decades with great success. The Ad vaccines are safe, effective, and economical. In an effort to extend the advantages of live Ad to immunization against malaria, a replicating recombinant Ad vector has been constructed that displays a protective peptide epitope from the Plasmodium falciparum circumsporozoite protein (CSP) on the Ad virus capsid. Previous studies showed that this recombinant virus induced high titers of sporozoite-neutralizing antibodies in mice, which encouraged the non-human primate immunization studies currently underway. In my current project, I have shown that immunization of Aotus nancymaae new-world monkeys induced anti-CSP antibodies detectable by ELISA in four of four animals. Antibodies from one animal showed in vitro neutralization activity. These results suggest that capsid display recombinants may provide a route to immunization against malaria and other diseases.

Adenoviruses are also powerful models for investigation of virus-host interactions and cellular biology. The dsDNA virus usurps or inactivates many cellular pathways to create an intracellular environment more amenable for viral growth. For example, my graduate work demonstrated the role of inhibition of the double-strand break repair (DSBR) response in protection of the incoming linear, Ad genome from inactivation by DSBR. Adenoviruses also modify intracellular mRNA metabolism, in part by disruption of regulatory structures (P-bodies) by a direct interaction between the Ad protein E4 11k and a main P-body component, Ddx6. This disruption is hypothesized to play a role in regulation of late viral gene expression. I plan to do future studies to explore the interaction between E4 11k and Ddx6 to determine the mechanism and function of the disruption of P-bodies. P-bodies are a common target of viruses, and an expansion to study these interactions will be explored as well.

For further information: or phone 278-2001
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