Abstract
In the present study we evaluated the protection raised by immunization with recombinant influenza viruses carrying sequences coding for polypeptides corresponding to medial and carboxi-terminal moieties of Trypanosoma cruzi ´s amastigote surface protein 2 (ASP2). Those viruses were used in sequential immunization with recombinant adenovirus (heterologous prime-boost immunization protocol) encoding the complete sequence of ASP2 (Ad-ASP2) in two mouse strains (C57BL/6 and C3H/He). The CD8 effector response elicited by this protocol was comparable to that observed in mice immunized twice with Ad-ASP2 and more robust than that observed in mice that were immunized once with Ad-ASP2. Whereas a single immunization with Ad-ASP2 sufficed to completely protect C57BL/6 mice, a higher survival rate was observed in C3H/He mice that were primed with recombinant influenza virus and boosted with Ad-ASP2 after being challenged with T. cruzi. Analyzing the phenotype of CD8+ T cells obtained from spleen of vaccinated C3H/He mice we observed that heterologous prime-boost immunization protocol elicited more CD8+ T cells specific for the immunodominant epitope as well as a higher number of CD8+ T cells producing TNF-α and IFN-γ and a higher mobilization of surface marker CD107a. Taken together, our results suggest that immunodominant subpopulations of CD8+ T elicited after immunization could be directly related to degree of protection achieved by different immunization protocols using different viral vectors. Overall, these results demonstrated the usefulness of recombinant influenza viruses in immunization protocols against Chagas Disease.
Highlights
Over a hundred years after its first description, Chagas Disease remains as an important public health problem, mostly in Latin America
Recombinant viruses carrying foreign sequences have been proven to be useful tools as vaccines against many pathogens, including those which require the induction of potent type I T cell immune responses, such as Leishmania s.p., Toxoplasma gondii and Trypanosoma cruzi [39]
Studies carried out by our group demonstrated that two immunizations with recombinant adenovirus carrying T. gondii or T. cruzi antigens were able to elicit specific humoral and cellular immune response and to protect different mouse lineages after challenge with those protozoan parasites [18,37]
Summary
Over a hundred years after its first description, Chagas Disease remains as an important public health problem, mostly in Latin America. To WHO, there are currently over 10 million people infected in Latin America and more than 100 million people live at risk areas in endemic countries. This disease kills approximately 13 thousand people every year, due to the clinical complications and to the poor efficacy of the pharmacological treatment which is highly toxic and effective mostly during the acute phase of disease [3,4]. The development of vaccines is an important approach to be used in therapy and prophylaxis of Chagas disease [3,8]
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