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Covalent vaccination with Trypanosoma cruzi Tc24 induces catalytic antibody production
Author(s) -
Gunter Sarah M.,
Versteeg Leroy,
Jones Kathryn M.,
Keegan Brian P.,
Strych Ulrich,
Bottazzi Maria Elena,
Hotez Peter J.,
Brown Eric L.
Publication year - 2018
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12585
Subject(s) - biology , trypanosoma cruzi , antibody , recombinant dna , chagas disease , immunization , antigen , microbiology and biotechnology , immunology , virology , biochemistry , gene , computer science , parasite hosting , world wide web
Summary Trypanosoma cruzi 24 (Tc24) is a recently described B‐cell superantigen (BC‐SAg) expressed by all developmental stages of T . cruzi , the causative agent of Chagas disease. BC ‐ SA gs are immunoevasins that interfere with the catalytic response available to a subset of natural antibodies comprising the preimmune (innate) repertoire. Electrophilic modifications of BC ‐ SA gs facilitate the formation of highly energetic covalent reactions favouring B‐cell differentiation instead of B‐cell downregulation. Therefore, the aim of this study was to convert the inhibitory signals delivered to B‐cells with specificity for Tc24 into activating signals after conjugating electrophilic phosphonate groups to recombinant Tc24 (eTc24). Covalent immunization with eT c24 increased the binding affinity between eTc24 and naturally nucleophilic immunoglobulins with specificity for this BC‐SAg. Flow cytometric analyses demonstrated that eTc24 but not Tc24 or other electrophilically modified control proteins bound Tc24‐specific IgM + B‐cells covalently. In addition, immunization of mice with eTc24 adjuvanted with ISA 720 induced the production of catalytic responses specific for Tc24 compared to the abrogation of this response in mice immunized with Tc24/ ISA 720. eTc24‐immunized mice also produced IgMs that bound recombinant Tc24 compared to the binding observed for IgMs purified from non e Tc 24‐immunized controls. These data suggest that e Tc 24 immunization overrides the immunosuppressive properties of this BC‐SAg.