Cysteine proteinase type I, encapsulated in solid lipid nanoparticles induces substantial protection against Leishmania major infection in C57BL/6 mice.
ABSTRACT Appropriate adjuvant, proper antigen(s) and a suitable formulation are required to develop stable, safe and immunogenic vaccines. Leishmanial cysteine proteinase type I (CPB) is a promising vaccine candidate; nevertheless, it requires a delivery system to induce a potent immune response. Herein, solid lipid nanoparticles (SLN) have been applied for CPB [with and without C-terminal extension (CTE)] formulation to utilize as a vaccine against Leishmania major infection in C57BL/6 mice. Therefore, SLN-CPB and SLN-CPB(-CTE) formulations were prepared from cetyl palmitate and cholesterol, using melt emulsification method. After intraperitoneal vaccination and subsequent L. major challenge, a strong antigen-specific T-helper type 1 (Th1) immune response was induced compared to control groups. Lymph node cells from immunized mice displayed lower parasite burden, higher IFN-γ, IgG2a and lower IL-4 production, indicating that robust Th1 immune response had been induced. Our results revealed that CTE is not necessary for inducing protective responses against L. major infection as the IFN-γ/IL-4 ratio was significantly higher, whereas IgG1 responses were lower in the SLN-CPB(-CTE) vaccinated group, post-challenge. Thus, SLN-CPB(-CTE) was shown to induce specific Th1 immune responses to control L. major infection, through effective antigen delivery to the peritoneal antigen presenting cells.
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ABSTRACT: We developed a microtitration method to determine the parasite burdens in homogenized organs of mice infected with Leishmania infantum. This method proved more sensitive than direct enumeration of amastigotes in stained organs, was appropriate for describing the kinetics of infection, and can be considered for physiopathological or pharmaceutical experimental studies.Antimicrobial Agents and Chemotherapy 10/1995; 39(9):2167-8. · 4.57 Impact Factor
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ABSTRACT: Comparative protein modeling is increasingly gaining interest since it is of great assistance during the rational design of mutagenesis experiments. The availability of this method, and the resulting models, has however been restricted by the availability of expensive computer hardware and software. To overcome these limitations, we have developed an environment for comparative protein modeling that consists of SWISS-MODEL, a server for automated comparative protein modeling and of the SWISS-PdbViewer, a sequence to structure workbench. The Swiss-PdbViewer not only acts as a client for SWISS-MODEL, but also provides a large selection of structure analysis and display tools. In addition, we provide the SWISS-MODEL Repository, a database containing more than 3500 automatically generated protein models. By making such tools freely available to the scientific community, we hope to increase the use of protein structures and models in the process of experiment design.Electrophoresis 12/1997; 18(15):2714-23. · 3.26 Impact Factor
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ABSTRACT: Trypanosomes and Leishmania contain an abundance of stage-regulated cysteine proteinases encoded by several gene families. Analysis of parasites rendered defective in cysteine proteinase function, either through genetic manipulation or through the use of specific inhibitors, has revealed roles for the enzymes in parasite virulence, in modulation of the host's immune response and in parasite differentiation.Current Opinion in Microbiology 09/1998; 1(4):455-60. · 8.23 Impact Factor