Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease

Abstract

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Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection

“…The protection was associated with increase of CD8 + T cell proliferation and IFN-γ production [31,32]. However, these same candidates did not control cardiomyopathy in chronically infected mice or dogs (reviewed in [18,33]). DNA therapy encoding ASP2 and TS (individually or in combination) offered no protection against parasite burden, mortality, and cardiomyopathy in infected mice [15,30], despite their known efficacy as a prophylactic vaccine.…”

Cruzipain and Its Physiological Inhibitor, Chagasin, as a DNA-Based Therapeutic Vaccine Against Trypanosoma cruzi

“…This immunotherapeutic vaccine not only would allow targeting different humoral and cellular elements as well metabolic pathways but also would be able to reduce doses and drug exposure periods, thus contributing to the decrease in toxic effects and minimization of the emergence of drug resistance. Not to be underestimated, as has been recently reviewed by Rios et al ( 61 ) and proposed by Dumonteil et al ( 62 ), therapeutic vaccines could be an excellent tool to avoid future congenital transmission, which is estimated at 5% in Latin America, preventing the risk of pregnancy complications like preterm rupture of membranes and preterm delivery. Although available drugs are not approved for use during pregnancy, several studies suggest that reducing maternal parasitemia before conception reduces the risk of congenital transmission ( 63 – 65 ), and it was recently estimated that a therapeutic vaccination of Chagas-positive pregnant women would be cost-effective and cost saving ( 66 ).…”

O desenvolvimento de vacinas contra as doenças tropicais negligenciadas

“…Together with adjuvant E6020, Tc24 showed that 60% of therapeutically vaccinated mice had undetectable levels of parasite and decreased cardiac fibrosis. Greater efficiency was also observed in the therapeutic vaccine TG2/TcG4 in infected animals that overexpressed glutathione peroxidase and that were able to control oxidative damage responses 20,22,24 .…”

“…Other antigens that do not belong to large families and that have been tested for their antigenic potential include the complementary regulatory protein (CRP or gp160); the lysosomal cysteine proteinase called cruzipain (60kDa); the calcium flagellar binding proteins FCaBP or Tc24 (24kDa) and GP82 (82kDa); the kinetoplastids membrane proteins KMP-11 (11kDa) and LYT1 (61kDa), and the paraflagellar rod proteins (70-86kDa) and TC52 (52kDa). Along with vaccine candidates, multiple adjuvants, administration routes, concentration and number of doses, and prime boost strategies are also being tested to change immune responses induced by the Th1 vaccine and improve long-term protective efficacy 20,22 .…”