Revealing the attenuating mutations of F. tularensis                              LVS

Recombinant Antigen-based Assays for Flavivirus                              Serodiagnosis and                              Surveillance

Identification and Inhibition of Cytokines Induced                              During OHFV Infection

Cell Wall Proteins in Bacillus anthracis as
                      Vaccines

Rational Design and Optimization of New Live-                              attenuated Vaccines for                              Alphaviral Enciphalitides

Nodavirus-based RNA Replicon Vaccines for                              Tick-borne Encephalitis                               Virus

Antiviral Agents as Therapy for SARS

Typhus Group Rickettsial Antigens Recognized by                              CD8+ T Lymphocytes

Revealing the attenuating mutations of F. tularensis LVS

Institution: Baylor College of Medicine, Houston, TX

Principal Investigator: Joseph Petrosino, Ph.D.

Co-Investigators:
a) George Weinstock, Ph.D. – Baylor College of Medicine, Human Genome Sequencing Center, Houston, TX
b) Rebecca Morton, D.V.M., Ph.D. – Oklahoma State University, Center for Veterinary Health Science, Stillwater, OK
c) Kenneth Clinckenbeard – Oklahoma State University, Center for Veterinary Health Science, Stillwater, OK

Expected Product: Identification of potential genetic causes for attenuation in LVS that will impact vaccine development for tularemia.

Description: Francisella tularensis is one of the most infectious bacteria known and is a serious bioterrorism threat. A weakened strain (named LVS) has proven to be an effective vaccine for this organism in humans, but is not approved for use in the U.S., in part because its mechanism of attenuation is unknown. Based on genetic comparisons with a parental virulent strain, we have found relatively few genetic candidates for attenuation. Subsequent experiments in an infection model will test which genetic differences underlie the attenuating mechanism in LVS. This data may help lead to U.S. approval of the LVS vaccine and will help in the design of additional attenuated vaccine strains for Francisella and other pathogens.