Abstract
Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all Leishmania species. To overcome this problem, we selected six potentially immunogenic peptides derived from Leishmania histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures. We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against L. braziliensis or L. infantum. Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected in vitro with L. braziliensis or L. infantum. The peptide mix generated the IFN-γ, IL-12, IL-4 and TGF-β that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that the mix of peptides derived from histone and parasites membrane molecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.
Highlights
Despite all the advances in the field of immunization and different strategies to identify new antigenic molecules, there is still no antigen capable of inducing Leishmania spp. control and protecting individuals against leishmaniosis
The proteins HP1 and HP2 from L. amazonensis were compared with the protein HP6 from L. braziliensis; all three proteins correspond to the histone subunit H3
The parameters of similarity and identity were not analyzed for HP3, because the protein sequence of histone subunit fraction H1 was not found for L. braziliensis and L. infantum
Summary
Despite all the advances in the field of immunization and different strategies to identify new antigenic molecules, there is still no antigen capable of inducing Leishmania spp. control and protecting individuals against leishmaniosis. It is essential to search for new technologies to develop antigen candidates for diagnosis or a vaccine to induce the control of these diseases in individuals who reside in at risk regions (De Brito et al, 2018) Given this scenario, an attractive alternative is peptidebased antigens that use epitopes of immunogenic proteins, which can stimulate a long-lasting immune response against the pathogen. Antigens can be characterized as chemical molecules, similar to classical drugs, their production is reproducible, simple, costeffective and fast, and low cost to scale-up (Joshi et al, 2014) Concerning immunity, these antigens can be customizing to generate specific responses and can be combined to design multiepitopes or multi-specific antigens to target different Leishmania species or immunogenic molecules from different stages of the parasite life cycle. One of the strategies to overcome this challenge is to design a multi-epitope-based antigen, which consists of incorporating multiple epitopes that allows for better coverage of natural pathogen antigen diversity (Moyle and Toth, 2013; De Brito et al, 2018)
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