HisAK70: progress towards a vaccine against different forms of leishmaniosis.

Javier Carrión,Abel Martínez-Rodrigo,Gustavo Domínguez-Bernal,Alicia Mas,Pilar Horcajo,José A Ruiz-Santa-Quiteria,José A Orden,Ricardo De La Fuente,Lara Ordóñez-Gutiérrez

doi:10.1186/s13071-015-1246-y

Abstract

BackgroundLeishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd.MethodsHere, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL.ResultsHisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model.ConclusionsThe results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.

Highlights

Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively
We focus on seven Leishmania Ag (the four core histones, A2, KMP11 and 70 kDa heat shock protein (HSP70)) that have already been successfully tested as DNA vaccines against CL or VL [22, 27]
HisAK70 protein can be expressed in CHO-K1 cells The expression of HisAK70 in CHO-K1 cells transfected with pVAX1::HisAK70-asd was detected using a mouse monoclonal anti-Leishmania A2 antibody and Epitope tag (E-Tag) was detected by monoclonal HRP/ anti-E Tag Conjugate (Fig. 2)

Summary

Introduction

Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. The leishmanioses cover a range of vector-borne diseases caused by infection with various species of intracellular protozoan parasites of the genus Leishmania [1]. The leishmanioses represent the secondlargest parasitic killer in the world after malaria [12]. Leishmania major in the Old World, and L. infantum (= L. chagasi) in the Mediterranean region of the Old World and in the Americas [14, 15] are Domínguez-Bernal et al Parasites & Vectors (2015) 8:629 among the main species that are responsible for CL and VL, respectively. Canine leishmaniosis is endemic in the Mediterranean basin, and is a public health problem which should be tackled [16, 17]

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