Vaccination with the Leishmania major ribosomal proteins plus CpG oligodeoxynucleotides induces protection against experimental cutaneous leishmaniasis in mice

Abstract

In the present work we analyze the antigenicity of Leishmania major ribosomal proteins (LRP) in infected BALB/c mice. We show that BALB/c mice vaccinated with LRP in the presence of CpG oligodeoxynucleotides (CpG-ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load after challenge with L. major. This protection was associated with the induction of an IL-12 dependent specific-IFN-gamma response mediated mainly by CD4(+) T cell, albeit a minor contribution of CD8(+) T cells cannot be ruled out. Induction of Th1 responses against LRP also resulted in a reversion of the Th2 responses associated with susceptibility. A marked reduction of IgG1 antibody titer against parasite antigens besides an impaired IL-4 and IL-10 cytokine production by parasite specific T cells was observed. In addition, we show that the administration of the LRP plus CpG-ODN preparation also conferred protection in the naturally resistant C57BL/6 mice. In this strain protection was associated with a LRP specific IFN-gamma production in lymph nodes draining the challenge site. We believe that these evolutionary conserved proteins, combined with adjuvants that favor Th1 responses, may be relevant components of a pan-Leishmania vaccine.

Specific Serodiagnosis of Canine Visceral Leishmaniasis Using Leishmania Species Ribosomal Protein Extracts

“…In addition, Leishmania ribosomal proteins (LRPs) seem to be immunologically relevant molecules during murine experimental cutaneous leishmaniasis because high titers of antibodies recognizing the parasite ribosomal proteins were detected in sera from BALB/c mice infected with L. major (28). Here, we show that sera from dogs naturally infected with L. infantum showed reactivity against different ribosomal proteins by Western blotting.…”

“…Since the antigenicity of the parasite ribosomal proteins was also demonstrated in mouse models of cutaneous leishmaniasis (28), it can be deduced that parasite ribosomes interact with the immune system of the vertebrate hosts during natural and experimental Leishmania infections. Parasite ribosomal proteins were employed as the source of antigen for ELISA, a precise and sensitive technique for the screening of a large number of samples for the diagnosis of VL (21,44).…”

“…LRP was prepared from logarithmic-phase promastigotes of L. infantum, as described previously (28). Briefly, 1 ؋ 10 9 promastigotes were harvested, washed twice in prechilled PBS, resuspended in 1 ml Nonidet P-40 lysis buffer (10 mM Tris HCl, pH 8.0, 150 mM NaCl, 1.5 mM MgCl 2 , 0.5% Nonidet P-40), and pipetted up and down 10 times.…”

CpG Oligodeoxynucleotide 2006 and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

“…The use of CpG-ODN against leishmaniasis has been reported, especially its use as an immunomodulator or adjuvant with various immunogens (2,8,12,22). Its sequence is 5Ј-TCG TCG TTT TGT CGT TTT GTC GTT-3Ј (21), and it is known for having better efficacy in human models (14).…”

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).…”