Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies

Brito, Rory C F; Guimarães, Frederico Gonçalves; Velloso, João Paulo Linhares; Corrêa-Oliveira, Rodrigo; Ruiz, Jerônimo C.; Reis, Alexandre Barbosa; Resende, Daniela de Melo

doi:10.3390/ijms18020371

Cited by 23 publications

(22 citation statements)

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“…Epitope mapping in proteomes of parasites is much more complex than the mapping of epitopes in proteins already described as immunogenic [21,22]. In this way, the use of the integrative approach to immunoinformatics proposed by Brito, Guimaraes, Velloso, Correa-Oliveira, Ruiz, Reis and Resende [7] was important to achieve potential epitopes in this study. After employing the immunoinformatics methodologies, we identified MHC class I and class II ligand epitopes comprising mouse and human alleles, due to the absence of predictors comprising dog alleles.…”

Section: Discussionmentioning

confidence: 96%

“…(1) Selection of linear epitopes for T-cells based on a pipeline described by Brito et al (2017) [7]: This pipeline was used to map the whole L. infantum predicted proteome, comprising the selection of potential proteins that have a consensus of predicted binding epitopes to major histocompatibility complex (MHC) class I and II, B cell epitopes, and specific subcellular locations. Thus, from the results of different immunoinformatics approaches employed, we constructed a relational database integrating the data of the L. infantum predicted proteome.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the published study concerning the mapping of potential Leishmania antigens through immunoinformatics [7], six L. infantum proteins from the predicted proteome were selected as candidate antigens. To avoid autoimmunity responses, peptides were checked for similarity with human, dog, and mouse proteomes.…”

Section: In Silico Analysis Of L Infantum Predicted Proteomementioning

confidence: 99%

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Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB/c Mice

et al. 2019

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Reverse vaccinology or immunoinformatics is a computational methodology which integrates data from in silico epitope prediction, associated to other important information as, for example, the predicted subcellular location of the proteins used in the design of the context of vaccine development. This approach has the potential to search for new targets for vaccine development in the predicted proteome of pathogenic organisms. To date, there is no effective vaccine employed in vaccination campaigns against visceral leishmaniasis (VL). For the first time, herein, an in silico, in vitro, and in vivo peptide screening was performed, and immunogenic peptides were selected to constitute VL peptide-based vaccines. Firstly, the screening of in silico potential peptides using dogs naturally infected by L. infantum was conducted and the peptides with the best performance were selected. The mentioned peptides were used to compose Cockt-1 (cocktail 1) and Cockt-2 (cocktail 2) in combination with saponin as the adjuvant. Therefore, tests for immunogenicity, polyfunctional T-cells, and the ability to induce central and effector memory in T-lymphocytes capacity in reducing the parasite load on the spleen for Cockt-1 and Cockt-2 were performed. Among the vaccines under study, Cockt-1 showed the best results, eliciting CD4+ and CD8+ polyfunctional T-cells, with a reduction in spleen parasitism that correlates to the generation of T CD4+ central memory and T CD8+ effector memory cells. In this way, our findings corroborate the use of immunoinformatics as a tool for the development of future vaccines against VL.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: In Silico Analysis Of L Infantum Predicted Proteomementioning

confidence: 99%

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Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB/c Mice

et al. 2019

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“…Currently, it is possible to scan entire genomes searching for candidates and to select them to be tested as vaccines [ 44 ], and with the advent of reverse vaccinology, a significant effort has been made to provide predictor programs of new molecules with distinct biotechnological applications [ 45 , 46 ]. However, the bottleneck in this workflow analysis is the validation of predictions for protozoan parasites [ 47 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Small Myristoylated Protein-3, Identified as a Potential Virulence Factor in Leishmania amazonensis, Proves to be a Protective Antigen against Visceral Leishmaniasis

Pires-Oliveira

Martins

Santos

et al. 2018

IJMS

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In a proteomics approach conducted with Leishmania amazonensis, parasite proteins showed either an increase or a decrease in their expression content during extensive in vitro cultivation, and were related to the survival and the infectivity of the parasites, respectively. In the current study, a computational screening was performed to predict virulence factors among these molecules. Three proteins were selected, one of which presented no homology to human proteins. This candidate, namely small myristoylated protein-3 (SMP-3), was cloned, and its recombinant version (rSMP-3) was used to stimulate peripheral blood mononuclear cells (PBMCs) from healthy subjects living in an endemic area of leishmaniasis and from visceral leishmaniasis patients. Results showed high interferon-γ (IFN-γ) production and low levels of interleukin 10 (IL-10) in the cell supernatants. An in vivo experiment was then conducted on BALB/c mice, which were immunized with rSMP-3/saponin and later challenged with Leishmania infantum promastigotes. The rSMP-3/saponin combination induced high production of protein-specific IFN-γ, IL-12, and granulocyte-macrophage colony-stimulating factor (GM-CSF) by the spleen cells of the immunized mice. This pattern was associated with protection, which was characterized by a significant reduction in the parasite load in distinct organs of the animals. Altogether, these results have revealed that this new virulence factor is immunogenic in both mice and humans, and have proven its protective efficacy against visceral leishmaniasis in a murine model.

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“…Various studies have since been performed using peptide epitope predictions in previously known immunogenic proteins. These algorithms have become more powerful in predicting epitopes, and they can be combined to increase the accuracy for large-scale peptide epitope predictions in Leishmania proteomes ( 57 , 58 ). Thus, today it is possible to perform high-throughput screening in whole Leishmania proteomes and identify peptides that elicit protective immune responses in vitro as well as in vivo ( 43 , 53 ).…”

Section: Leishmanial Peptide-based Vaccinesmentioning

confidence: 99%

Peptide Vaccines for Leishmaniasis

et al. 2018

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Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

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Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies

Cited by 23 publications

References 62 publications

Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB/c Mice

Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB/c Mice

Small Myristoylated Protein-3, Identified as a Potential Virulence Factor in Leishmania amazonensis, Proves to be a Protective Antigen against Visceral Leishmaniasis

Peptide Vaccines for Leishmaniasis

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