Epidemic Typhus

This strain is the virulent ancestor of the previously sequenced attenuated R. prowazekii Madrid E strain. Comparison of these two genome sequences should illuminate the site(s) of mutation that have led to attenuation and allow a stably attenuated vaccine strain to be developed.

Epidemic typhus, caused by Rickettsii prowazekii, is one of man's greatest scourges in the last 500 years of history. It occurs currently in areas with social disorder and/or poor economic conditions. R. prowazekii is a category B priority potential bioterror pathogen. There is no safe vaccine for preventing epidemic typhus. The long term goal of this project is to understand the pathogenesis of rickettsial diseases and to prevent epidemic typhus. Epidemic typhus can be prevented by vaccination with the attenuated E strain (also called Madrid E strain). However, E strain is not used for vaccination because it causes mild epidemic typhus in 14% of immunized persons apparently due to reversion to the virulent Evir strain. We hypothesize that a reverse mutation occurred in Evir strain and is the determinant for the virulence of Evir strain and that a knockout of the mutated gene in E strain will prevent the reverse mutation. The objective of this project is to develop an effective and safe vaccine for epidemic typhus.

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Contacts

Name	Affiliation
Patrick Minx	The Genome Institute, Washington University School of Medicine

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