Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine

AUGUSTO ERNESTO BIVONA; ANDRÉS SÁNCHEZ ALBERTI; MARINA NADIA MATOS; NATACHA CERNY; ALEJANDRO CARDOSO; CELINA MORALES; GERMÁN GONZÁLEZ; SILVIA I. CAZORLA; EMILIO LUIS MALCHIODI

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018

1935-2735

Chagas disease, also known as American Trypanosomiasis, is a chronic parasiticdisease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people over the world and more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial. Thus, prophylactic and/or therapeutic vaccines are emerging as interesting control alternatives. In this work, we proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a new antigen for vaccine development against Chagasdisease. Methodology/Principal FindingsIn a murine model, we analyzed the immune response triggered by differentimmunization protocols based on Tc80 and evaluated their ability to confer protection against a challenge with the parasite. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, neutralization of parasite infection and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α) upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T lymphocyte activity against one Tc80 MHCI peptide.Immunization protocols conferred protection against a T. cruzi lethal challenge.Immunized groups showed a decreased parasitemia and higher survival rate than nonimmunized control mice. Moreover, in a chronic infection model, immunized mice presented: lower levels of myopathy-linked enzymes, parasite burden,electrocardiographic disorders and inflammatory cells. Conclusions/SignificanceConsidering that an early control of parasite burden and tissue damage mightcontribute to avoid the progression towards symptomatic forms of chronic Chagasdisease, the efficacy of Tc80-based vaccines make this molecule a promisingimmunogen for a mono or multicomponent vaccine against T. cruzi infection.