Vaccination with the Leishmania infantum ribosomal proteins induces protection in BALB/c mice against Leishmania chagasi and Leishmania amazonensis challenge

Abstract

Leishmania chagasi and Leishmania amazonensis are the etiologic agents of different clinical forms of human leishmaniasis in South America. In an attempt to select candidate antigens for a vaccine protecting against different Leishmania species, the efficacy of vaccination using Leishmania ribosomal proteins and saponin as adjuvant was examined in BALB/c mice against challenge infection with both parasite species. Mice vaccinated with parasite ribosomal proteins purified from Leishmania infantum plus saponin showed a specific production of IFN-γ, IL-12 and GM-CSF after in vitro stimulation with L. infantum ribosomal proteins. Vaccinated mice showed a reduction in the liver and spleen parasite burdens after L. chagasi infection. After L. amazonensis challenge, vaccinated mice showed a decrease of the dermal pathology and a reduction in the parasite loads in the footpad and spleen. In both models, protection was correlated to an IL-12-dependent production of IFN-γ by CD4(+) and CD8(+) T cells that activate macrophages for the synthesis of NO. In the protected mice a decrease in the parasite-mediated IL-4 and IL-10 responses was also observed. In mice challenged with L. amazonensis, lower levels of anti-parasite-specific antibodies were detected. Thus, Leishmania ribosomal proteins plus saponin fits the requirements to compose a pan-Leishmania vaccine.

Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when in association with the recombinant LiHyp1 protein, to protect against visceral leishmaniasis

“…+ and CD8 + cell subsets may be important for the killing of parasites in vaccinated mice using several parasite recombinant antigens (Chávez-Fumagalli et al, 2010;Costa et al, 2014;Martins et al, 2013), the present study's data suggest that CD8 + cells may contribute to a lesser extent to the induction of an IFN-γ-mediated response elicited by immunization using the rLiHyp1 protein, when the immunogen was evaluated in association with different adjuvants.…”

“…In the present study, immunized mice produced higher levels of Leishmania-specific IgG2a antibodies, as compared to IgG1 levels, also demonstrating the development of a Th1 immune response in these animals. As observed in the IFN-γ and IL-12 production, spleen cells from vaccinated mice produced higher levels of GM-CSF, a cytokine related to macrophage activation and resistance in murine models against intracellular pathogens, such as L. infantum (Chávez-Fumagalli et al, 2010), L. major (Dumas et al, 2003), and L. donovani (Murray et al, 1995).…”

“…Additionally, in vaccine studies, immunogens are administered in association with Th1-type adjuvants and, after only a few weeks, mice are infected and followed-up for about 2 or 3 months (Chávez-Fumagalli et al, 2010;Costa et al, 2014;Martins et al, 2013). In this time, spleen cells are collected and cultured in vitro with the antigens used in the immunization protocols, and/or with Leishmania extracts, in order to evaluate their immunogenicity.…”

“…The evidence of life-long immunity has inspired the development of vaccination protocols against the disease, but few have progressed beyond the experimental stage (Chávez-Fumagalli et al, 2010;Coelho et al, 2003;Costa et al, 2014;Ramírez et al, 2013Ramírez et al, , 2014. In these studies, the type-1 cell-mediated immunity has proven to be important as a protective response against leishmaniasis.…”

Biología sintética: aspectos científicos y sociales

“…Una vacuna de este tipo induce protección total contra L. major en ratones 57BL/6. Se ha observado igualmente que la vacunación de ratones con una mezcla de proteínas ribosomales induce respuestas de tipo Th1 junto a la generación de respuestas protectivas y se correlaciona con protección contra L. major (Iborra et al, 2008), L. amazonensis o L. Chagasi (Chávez-Fumagalli et al, 2010). La protección observada en el modelo BALB/c-L. major fue tan robusta que resistió una segunda infección (Ramirez et al, 2013).…”