IN VIVO MURINE IMMUNE MODULATION IN RESPONSE TO ATTENUATED TRYPANOSOMA CRUZI INFECTION AND QUIL-A ADJUVANT ADMINISTRATION

ZABALA, BRENDA ANDREA; VAZQUEZ, MARIA ELISA; ANDREA C. MESIAS; ACUÑA, LEANDRO; CECILIA PEREZ BRANDAN

Salta

Congreso; Joint LV Annual SAIB Meeting and XIV PABMB Congress; 2019

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Several immunoprophylactic attempts have been made in order to prevent the establishment and persistence in the host of Trypanosoma cruzi, the etiologic agent of Chagas disease (CD). Notwithstanding, up to date there are no vaccines for human application. Most assessed protocols included heterologous, prime-boost immunization schemes based on combination of subunits such us recombinant proteins and nucleic acids. These formulations are less immunogenic than live attenuated vaccines. Further, adjuvants are key components as they enhance and modulate the immune response against vaccine antigens. In our laboratory, we have extensively studied the attenuated TCC strain of T. cruzi and we have recorded the immune response profile of different animal models inoculated with these parasites. Our goal is to study live parasites based-formulations when adding Quil-A adjuvant (TCC+Quil-A), in order to evaluate the combination as an experimental immunogen against CD. We performed a murine immunization scheme using metacyclic trypomastigotes formulated with Quil-A. During the vaccination stage, an increase in IL-10 and IFN-γ production was detected in stimulated spleen cells of TCC-immunized animals when compared with non immunized control group. Distinctly, we noted that IFN-γ levels increased and IL-10 levels decreased in stimulated cells of animals that received TCC combined with Quil-A (vs. TCC). In relation to the humoral response, levels of anti-T.cruzi specific IgG1 and IgG2c antibodies were higher in TCC-immunized mice sera than in non immunized control group. IgG1 ratio was significantly higher from IgG2c when compared sera from animals treated with TCC+Quil-A in relationship to those inoculated only with TCC. After virulent challenge with Tulahuen blood trypomastigotes, parasitemias were almost undetectable in all immunized mice, whereas control groups (treated with PBS or Quil-A alone) showed high parasite load and died. Several factors are implicated in the modulation of the immune response and they still need to be tested in order to materialize the use of live parasites combined with specific adjuvants as a possible vaccine formulation. In summary, the results obtained so far indicate that Quil-A proved to be a modulator of the immune response elicited by TCC, triggering a balanced Th1/Th2 phenotype. Considering our previous results involving attenuated parasites immunizations as a prophylactic strategy for CD, we strongly support that it is worthy to continue working on multicomponent vaccines approaches.