CVI Accepts, published online ahead of print on 28 January 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00362-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Francisella tularensis infection-derived monoclonal antibodies provide detection, protection and therapy

Anne G. Savitt, Patricio Mena-Taboada, Gloria Monsalve, and Jorge L. Benach^*

Center for Infectious Disease, Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794

^* To whom correspondence should be addressed. Email: jbenach{at}notes.cc.sunysb.edu.

Francisella tularensis is the causative agent of tularemia, and a potential agent of biowarfare. As an easily transmissible infectious agent, rapid detection and treatment is necessary to provide a positive clinical outcome. As an agent of biowarfare, there is an additional need to prevent infection. We made monoclonal antibodies to the F. tularensis subsp. holarctica Live Vaccine Strain (Ft LVS) by infecting mice with a sublethal dose of bacteria, and, following recovery, by boosting the mice with sonicated organisms. The response to the initial and primary infection was restricted to IgM antibody directed solely against LPS. After boosting with sonicated organisms, the specificity repertoire broadened against protein antigens including DnaK, LpnA, FopA, bacterioferritin, the 50s ribosomal protein L7/L12 and metabolic enzymes. These monoclonal antibodies detect Ft LVS by routine immunoassays, including ELISA, western blot, and immunofluorescence. Ability of the antibodies to protect mice from intradermal infection, both prophylactically and therapeutically, was examined. An antibody to LPS was identified which provides complete protection from infection with Ft LVS and partial protection from infection with F. tularensis subsp. tularensis strain SchuS4. There was no bacteremia and reduced organ burden within the first 24 hours when mice were protected from Ft LVS infection with the anti-LPS antibody. No antibody was identified that provided complete protection when administered therapeutically; however, passive transfer of antibodies against LPS, FopA and LpnA resulted in 40 to 50% survival of mice infected with Ft LVS.

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