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Protective efficacy in a hamster model of a multivalent vaccine for human visce...

Fernández, L; Solana, JC; Sánchez, C; Jiménez, MÁ; Requena, JM; Coler, R; Reed, SG; Valenzuela, JG; Kamhawi, S; Oliveira, F; Fichera, E; Glueck, R

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if un-treated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the Leishmania membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the ...


Engineering a vector-based pan-Leishmania vaccine for humans: proof of principle

Cecílio, P; Oristian, J; Meneses, C; Serafim, TD; Valenzuela, JG; Cordeiro-da-Silva, A; Oliveira, F

Leishmaniasis is a spectrum of diseases transmitted by sand fly vectors that deposit Leishmania spp. parasites in the host skin during blood feeding. Currently, available treatment options are limited, associated with high toxicity and emerging resistance. Even though a vaccine for human leishmaniasis is considered an achievable goal, to date we still do not have one available, a consequence (amongst other fact...


More than just exosomes: distinct Leishmania infantum extracellular products po...

Perez-Cabezas, B; Santarém, N; Cecílio, P; Silva, C; Silvestre, R; A M Catita, J; Cordeiro-da-Silva, A

The use of secretion pathways for effector molecule delivery by microorganisms is a trademark of pathogenesis. Leishmania extracellular vesicles (EVs) were shown to have significant immunomodulatory potential. Still, they will act in conjunction with other released parasite-derived products that might modify the EVs effects. Notwithstanding, the immunomodulatory properties of these non-vesicular components and ...


Murine infection with bioluminescent Leishmania infantum axenic amastigotes app...

Costa, DM; Cecílio, P; Santarém, N; Cordeiro-da-Silva, A; Tavares, J

Leishmaniasis is an important vector-borne neglected tropical disease caused by Leishmania parasites. Current anti-Leishmania chemotherapy is unsatisfactory, justifying the continued search for alternative treatment options. Herein, we demonstrate that luciferase-expressing Leishmania infantum axenic amastigotes, unlike promastigotes, are highly infectious to BALB/c mice and thus generate a robust bioluminescen...


Understanding resistance vs. susceptibility in visceral leishmaniasis using mou...

Perez-Cabezas, B; Cecílio, P; Gaspar, TB; Gärtner, F; Vasconcellos, R; Cordeiro-da-Silva, A

Every year, up to 90,000 new cases of Visceral Leishmaniasis and 30,000 resultant deaths are estimated to occur worldwide. Such numbers give relevance to the continuous study of this complex form of the disease: a zoonosis and an anthroponosis; two known etiological agents (Leishmania infantum and L. donovani, respectively); with an estimated average ratio of 1 symptomatic per 10 asymptomatic individuals; and s...


Pre-clinical antigenicity studies of an innovative multivalent vaccine for huma...

Cecílio, P; Pérez-Cabezas, B; Fernández, L.; Moreno, J; Carrillo, E; Requena, J; Fichera, E; Reed, S; Coler, R; Kamhawi, S; Oliveira, F; Valenzuela, J

The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis...


Interleukin-27 early impacts Leishmania infantum infection in mice and correlat...

Pérez-Cabezas, B; Cecílio, P; Robalo, AL; Silvestre, R; Carrillo, E; Moreno, J; San, Martín J; Vasconcellos, R; Cordeiro-da-Silva, A

The complexity of Leishmania-host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused by Leishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two cla...


Disclosing the essentiality of ribose-5-phosphate isomerase B in Trypanosomatids

Faria, J; Loureiro, I; Santarém, N; Cecílio, P; Macedo-Ribeiro, S; Tavares, J; Cordeiro-da-Silva, A

Ribose-5-phosphate isomerase (RPI) belongs to the non-oxidative branch of the pentose phosphate pathway, catalysing the inter-conversion of D-ribose-5-phosphate and D-ribulose-5-phosphate. Trypanosomatids encode a type B RPI, whereas humans have a structurally unrelated type A, making RPIB worthy of exploration as a potential drug target. Null mutant generation in Leishmania infantum was only possible when an e...


Deception and manipulation: The arms of Leishmania, a successful parasite

Cecílio, P; Pérez-Cabezas, B; Santarém, N; Maciel, J; Rodrigues, V; Cordeiro-da-Silva, A

Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interacti...


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