A Human Type 5 Adenovirus-Based Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy

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The idea that Chagas disease (CD) has an important autoimmune involvement contributed to delay the development of therapies and vaccines. CD is a parasitic neglected disease which afflicts millions of people mostly in Latin America. The cardiac form is the main clinical manifestation of CD. Currently, patients with access to therapy receive medicaments that only mitigate symptoms. Because of the limited prospect of treatment, vaccine reemerged as a strategy to prevent infection, interfere with CD progression and, moreover, reverse heart abnormalities. Here we tested a recombinant adenovirus carrying sequences of ASP2 and TS T. cruzi antigens (rAdVax) as prophylactic and therapeutic tool using a model of chronic Chagas’ heart disease. We showed that prophylactic vaccination reduced heart parasite load, inflammation and electrical abnormalities. The rAdVax therapeutic vaccination also reduced heart injury and improved electrical function, preserved specific IFNγ-mediated immunity but reduced response to polyclonal stimuli, CD107a+ CD8+ T-cell frequency and plasma nitric oxide levels. Moreover, therapeutic rAdVax preserved the number IFNγ+ cells, but decreased perforin+ cells in the heart tissue. Therefore, our results support the hypothesis that vaccination can modify the immunological unbalance that concurs to Chagas’ heart disease to improve prognosis.

Vyšlo v časopise: A Human Type 5 Adenovirus-Based Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004594
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004594

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