Back to Search
Start Over
Covalent vaccination with Trypanosoma cruzi Tc24 induces catalytic antibody production.
- Source :
-
Parasite immunology [Parasite Immunol] 2018 Nov; Vol. 40 (11), pp. e12585. Date of Electronic Publication: 2018 Sep 24. - Publication Year :
- 2018
-
Abstract
- 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-SAgs are immunoevasins that interfere with the catalytic response available to a subset of natural antibodies comprising the preimmune (innate) repertoire. Electrophilic modifications of BC-SAgs 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 eTc24 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 <superscript>+</superscript> B-cells covalently. In addition, immunization of mice with eTc24 adjuvanted with ISA720 induced the production of catalytic responses specific for Tc24 compared to the abrogation of this response in mice immunized with Tc24/ISA720. eTc24-immunized mice also produced IgMs that bound recombinant Tc24 compared to the binding observed for IgMs purified from non eTc24-immunized controls. These data suggest that eTc24 immunization overrides the immunosuppressive properties of this BC-SAg.<br /> (© 2018 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Antibodies, Protozoan chemistry
Antibody Formation
B-Lymphocytes immunology
Chagas Disease diagnosis
Chagas Disease parasitology
Female
Humans
Immunization
Immunoglobulin M immunology
Mice
Mice, Inbred BALB C
Protozoan Proteins chemistry
Trypanosoma cruzi chemistry
Trypanosoma cruzi genetics
Vaccination
Antibodies, Catalytic immunology
Antibodies, Protozoan immunology
Chagas Disease immunology
Protozoan Proteins immunology
Trypanosoma cruzi immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-3024
- Volume :
- 40
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Parasite immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30132929
- Full Text :
- https://doi.org/10.1111/pim.12585