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Monoclonal antibodies identify different antigenic epitopes on the lipopolysaccharide of Francisella tularensis for potential use in immunotherapy of tularemia
Author(s) -
Roche Marly I.,
Lu Zhaohua,
Hui Julia H.,
Sharon Jacqueline
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.499
Subject(s) - francisella tularensis , tularemia , epitope , antibody , biology , monoclonal antibody , virology , isotype , antigen , microbiology and biotechnology , immunology , virulence , gene , biochemistry
The intracellular bacterium Francisella tularensis causes tularemia and is considered a biothreat. We had produced anti‐ F. tularensis IgG and IgM hybridoma antibodies for potential immunotherapy of tularemia. Several of the antibodies bound to F. tularensis lipopolysaccharide (LPS) and an LPS‐reactive antibody of the IgG2a isotype conferred protection against a lethal dose of F. tularensis live vaccine strain (LVS) in a mouse model of respiratory tularemia. To identify antibodies to non‐overlapping LPS epitopes, we determined the variable region nucleotide sequences of selected LPS‐reactive antibodies. Antibodies with unique sequences were then recombinantly converted into IgG2a and IgA, isotypes expected to be efficacious at conferring immunity to F. tularensis . The identities and LPS‐reactivity of two recombinant antibodies were confirmed by comparison to the original antibodies in ELISA and immunoblots. In a competition ELISA, based on isotype‐specific detection, these antibodies bound to an LPS epitope or overlapping LPS epitopes distinct from that targeted by the commercially available antibody FB11, specific for the O‐antigen of F. tularensis LPS. The expected synergy between our antibodies and FB11, and the efficacy of these antibodies against F. tularensis LVS and the pathogenic strain SchuS4 will be tested in the murine model of respiratory tularemia. Grant No U19AI56543