Design and Synthesis of IMR-23, an Oxime Derived from Nitroimidazole as an Immunomodulatory Molecule.

BACKGROUND: Adjuvants have been obtained empirically by trial and error experiments and today, there is a tendency to the rational design of adjuvants candidates, which will increasingly achieve effective and safe products. The aim of this work was to design and evaluate the compound IMR-23 derived from nitroimidazole as an immunomodulatory molecule. MATERIALS AND METHODS: The IMR-23 molecule was obtained by a condensation reaction, cytotoxicity was tested by the sulforhodamine B assay. Adjuvanticity was evaluated in vivo and in vitro in J774A.1 cells and in the mouse model, respectively. RESULTS: IMR-23 that did not show cytotoxicity on HeLa, Vero cells and macrophages J774A.1, was able to induce the production of molecules involved in the inflammatory process, such as cytokines and chemokines determined by ELISA, to induce the production of antibodies and to generate antigenspecific cells to ovalbumin and against the antigen GST-L1b. CONCLUSION: These results open the possibility of further studies to obtain a proper balance of immunogenicity- toxicity in the use of IMR-23 as an adjuvant molecule.

Highly discordant serology against Trypanosoma cruzi in central Veracruz, Mexico: role of the antigen used for diagnostic.

BACKGROUND: Chagas disease is a parasitic disease caused by the protozoan parasite Trypanosoma cruzi. In Mexico, the burden of the disease is difficult to estimate and improving surveillance for Chagas disease is an important priority. We aimed here at determining the seroprevalence of T. cruzi infection in humans in a rural community in Veracruz. METHODS: Serum samples (196) were analyzed for T. cruzi infection using five enzyme-linked immunosorbent assay (ELISA) tests: two in-house tests based on crude parasite extract and three commercial ELISA kits. Because of highly discordant results, we further explored the importance of parasite antigens and strains by western-blot analysis. RESULTS: A total of 74 samples (37.7 %) were reactive with at least one ELISA, but discordance among tests was very high. The best agreement was between Chagatest recombinant and Chagatek ELISA (Kappa index = 0.798). The agreement between other combinations of tests ranged from 0.038 to 0.518. Discordant samples were confirmed by western-blot analysis using up to nine parasite strains, giving a seroprevalence of 33.7 %. CONCLUSIONS: Commercial tests had a very limited ability to detect T. cruzi infection in the study population. In-house tests based on crude parasite antigens showed a greater sensitivity but were still unable to detect all cases of T. cruzi infection, even when based on a local parasite strain. The high seroprevalence confirmed the hyper-endemicity of T. cruzi infection in the region. Reliable epidemiological surveillance of Chagas disease will require the development of improved diagnostic tests.