Tumor Neoepitope-Based Vaccines: A Scoping Review on Current Predictive Computational Strategies.

Therapeutic cancer vaccines have been considered in recent decades as important immunotherapeutic strategies capable of leading to tumor regression. In the development of these vaccines, the identification of neoepitopes plays a critical role, and different computational methods have been proposed and employed to direct and accelerate this process. In this context, this review identified and systematically analyzed the most recent studies published in the literature on the computational prediction of epitopes for the development of therapeutic vaccines, outlining critical steps, along with the associated program's strengths and limitations.

Transcriptomic analysis of benznidazole-resistant and susceptible Trypanosoma cruzi populations.

Background: Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is a serious public health concern in Latin America. Nifurtimox and benznidazole (BZ), the only two drugs currently approved for the treatment of CD, have very low efficacies in the chronic phase of the disease and several toxic side effects. Trypanosoma cruzi strains that are naturally resistant to both drugs have been reported.

A specific Leishmania infantum polyepitope vaccine triggers Th1-type immune response and protects against experimental visceral leishmaniasis.

The development of an immunogenic, effective, and safe vaccine is essential as an alternative for disease control. The present study aimed to evaluate the immunogenicity and efficacy potential of a polyepitope T-cell antigen candidate against visceral leishmaniasis in a murine model. BALB/c mice were immunized with three doses subcutaneously with Poly-T Leish alone or adjuvanted with Saponin plus Monophosphoryl lipid A, with 15-day intervals between doses, and challenged with 10 stationary-phase Leishmania infantum promastigotes via tail vein.

Identification and characterization of microsatellite markers for population genetic studies of Panstrongylus megistus (Burmeister, 1835) (Triatominae: Reduviidae).

Background: Panstrongylus megistus is the most important vector of Chagas disease in Brazil. Studies show that the principal factor hindering the control of triatomines is reinfestation of houses previously treated with insecticides. Studies at the microgeographic level are therefore necessary to better understand these events.

Perspectives From Systems Biology to Improve Knowledge of Drug Resistance.

Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by different species and transmitted to humans by sandflies, are among such diseases. and other Trypanosomatidae display some peculiar features, which make them a complex system to study.

A chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice.

In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease.

Proteomic analysis reveals differentially abundant proteins probably involved in the virulence of amastigote and promastigote forms of Leishmania infantum.

Owing to the importance and clinical diversity of Leishmania infantum, studying its virulence factors is promising for understanding the relationship between parasites and hosts. In the present study, differentially abundant proteins from strains with different degrees of virulence in promastigote and amastigote forms were compared using two quantitative proteomics techniques, differential gel electrophoresis and isobaric mass tag labeling, followed by identification by mass spectrometry. A total of 142 proteins were identified: 96 upregulated and 46 downregulated proteins in the most virulent strain compared to less virulent.

Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow.

Bone marrow (BM) is an organ responsible for crucial processes in living organs, e. g., hematopoiesis.

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines.

Background: One of the major challenges to leishmaniasis treatment is the emergence of parasites resistant to antimony. To study differentially expressed genes associated with drug resistance, we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (Sb)-resistant Leishmania infantum lines using high-throughput RNA sequencing.

Methods: All the cDNA libraries were constructed from promastigote forms of each line, sequenced and analyzed using STAR for mapping the reads against the reference genome (L.

Hypervirulence and cross-resistance to a clinical antifungal are induced by an environmental fungicide in Cryptococcus gattii.

The increasing human population requires ongoing efforts in food production. This is frequently associated with an increased use of agrochemicals, leading to environmental contamination and altering microbial communities, including human fungal pathogens that reside in the environment. Cryptococcus gattii is an environmental yeast and is one of the etiological agents of cryptococcosis.

Diversity and genome mapping assessment of disordered and functional domains in trypanosomatids.

The proteins that have structural disorder exemplify a class of proteins which is part of a new frontier in structural biology that demands a new understanding of the paradigm of structure/function correlations. In order to address the location, relative distances and the functional/structural correlation between disordered and conserved domains, consensus disordered predictions were mapped together with CDD domains in Leishmania braziliensis M2904, Leishmania infantum JPCM5, Trypanosoma cruzi CL-Brener Esmeraldo-like, Trypanosoma cruzi Dm28c, Trypanosoma cruzi Sylvio X10, Blechomonas ayalai B08-376 and Paratrypanosoma confusum CUL13 predicted proteomes. Our results depicts the role of protein disorder in key aspects of parasites biology highlighting: a) statistical significant association between genome structural location of protein disordered consensus stretches and functional domains; b) that disordered protein stretches appear in greater percentage at upstream or downstream position of the predicted domain; c) a possible role of structural disorder in several gene expression, control points that includes but are not limited to: i) protein folding; ii) protein transport and degradation; and iii) protein modification.

Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis.

Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to spp.

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

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).

In silico analysis of putative dormancy genes in Plasmodium vivax.

Plasmodium vivax is the most widely spread species causing human malaria. The control of malaria caused by P. vivax has been largely hampered by its ability to develop a dormant liver stage that can generate a new blood infection at different periods of time.

TriatoKey: a web and mobile tool for biodiversity identification of Brazilian triatomine species.

Unlabelled: Triatomines are blood-sucking insects that transmit the causative agent of Chagas disease, Trypanosoma cruzi. Despite being recognized as a difficult task, the correct taxonomic identification of triatomine species is crucial for vector control in Latin America, where the disease is endemic. In this context, we have developed a web and mobile tool based on PostgreSQL database to help healthcare technicians to overcome the difficulties to identify triatomine vectors when the technical expertise is missing.

Identification and characterization of expressed retrotransposons in the genome of the Paracoccidioides species complex.

Background: Species from the Paracoccidioides complex are thermally dimorphic fungi and the causative agents of paracoccidioidomycosis, a deep fungal infection that is the most prevalent systemic mycosis in Latin America and represents the most important cause of death in immunocompetent individuals with systemic mycosis in Brazil. We previously described the identification of eight new families of DNA transposons in Paracoccidioides genomes. In this work, we aimed to identify potentially active retrotransposons in Paracoccidioides genomes.

Intrinsically disordered proteins (IDPs) in trypanosomatids.

Background: Proteins are composed of one or more amino acid chains and exhibit several structure levels. IDPs (intrinsically disordered proteins) represent a class of proteins that do not fold into any particular conformation and exist as dynamic ensembles in their native state. Due to their intrinsic adaptability, IDPs participate in many regulatory biological processes, including parasite immune escape.

Characterization of the small RNA content of Trypanosoma cruzi extracellular vesicles.

A growing body of evidence in mammalian cells indicates that secreted vesicles can be used to mediate intercellular communication processes by transferring various bioactive molecules, including mRNAs and microRNAs. Based on these findings, we decided to analyze whether Trypanosoma cruzi-derived extracellular vesicles contain RNA molecules and performed a deep sequencing and genome-wide analysis of a size-fractioned cDNA library (16-40nt) from extracellular vesicles secreted by noninfective epimastigote and infective metacyclic trypomastigote forms. Our data show that the small RNAs contained in these extracellular vesicles originate from multiple sources, including tRNAs.

The level of ascorbate peroxidase is enhanced in benznidazole-resistant populations of Trypanosoma cruzi and its expression is modulated by stress generated by hydrogen peroxide.

Ascorbate peroxidases (APX) are class I heme-containing enzymes that convert hydrogen peroxide into water molecules. The gene encoding APX has been characterized in 11 strains of Trypanosoma cruzi that are sensitive or resistant to benznidazole (BZ). Bioinformatic analysis revealed the presence of two complete copies of the T.

Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi.

Background: The Trypanosoma cruzi genome was sequenced from a hybrid strain (CL Brener). However, high allelic variation and the repetitive nature of the genome have prevented the complete linear sequence of chromosomes being determined. Determining the full complement of chromosomes and establishing syntenic groups will be important in defining the structure of T.

The TryPIKinome of five human pathogenic trypanosomatids: Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum--new tools for designing specific inhibitors.

Phosphatidylinositol (PI) kinases are at the heart of one of the major pathways of intracellular signal transduction. Herein, we present the first report on a survey made by similarity searches against the five human pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum genomes available to date for phosphatidylinositol- and related-kinases (TryPIKs). In addition to generating a panel called "The TryPIKinome", we propose a model of signaling pathways for these TryPIKs.

Phosphatidylinositol-and related-kinases: a genome-wide survey of classes and subtypes in the Schistosoma mansoni genome for designing subtype-specific inhibitors.

Phosphatidylinositol kinases (PIK) are at the heart of one of the major pathways of intracellular signal transduction. The signals made by PIK influence a wide variety of cellular functions, including cell growth, differentiation and survival, glucose metabolism and cytoskeletal organization. Wortmannin strongly binds in vitro to all PIK subtypes and it is therefore an effective antiproliferative agent.

Brazilian genome sequencing projects: state of the art.

This review covers all Brazilian Genome, EST and Metagenome Projects, Sequencing Networks' history and structure, and patents related to Brazilian Genome Projects, beginning with the first genome sequenced in this country, i.e. the 9a5c strain of Xylella fastidiosa CVC, up till the recently sequenced 1002 strain of Corynebacterium pseudotuberculosis, which was done with a mixed strategy that included both traditional Sanger methodology and Avant Garde 454 Life Sciences pyrosequencing technology.