Fundacion Institute Inmunologia Of Colombia Fidic

Bogotá, Colombia

Fundacion Institute Inmunologia Of Colombia Fidic

Bogotá, Colombia
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Perez-Cordero J.J.,National University of Colombia | Lozano J.M.,Fundacion Institute Inmunologia Of Colombia Fidic | Cortes J.,Autonomous University of Madrid | Delgado G.,National University of Colombia
Peptides | Year: 2011

Different species of Leishmania are responsible for cutaneous, mucocutaneous or visceral leishmaniasis infections in millions of people around the world [14]. The adverse reactions caused by antileishmanial drugs, emergence of resistance and lack of a vaccine have motivated the search for new therapeutic options to control this disease. Different sources of antimicrobial molecules are under study as antileishmanial agents, including peptides with antimicrobial and/or immunomodulatory activity, which have been considered to be potentially active against diverse species of Leishmania [7,39]. This study evaluated the cytotoxicity on dendritic cells, hemolytic activity, leishmanicidal properties on Leishmania panamensis and Leishmania major promastigotes and effectiveness on parasite intracellular forms (dendritic cells infected with L. panamensis and L. major promastigotes), when each parasite in culture was exposed to different concentrations of a group of synthetic peptides with previously reported antimicrobial properties, which were synthesized based on their naturally occurring reported sequences. Dermaseptin, Pr-2 and Pr-3 showed inhibitory activity on the growth of L. panamensis promastigotes, while Andropin and Cecropin A (with a selectivity index of 4 and 40, respectively) showed specific activity against intracellular forms of this species. The activities of Andropin and Cecropin A were exclusively against the intracellular forms of the parasite, therefore indicating the relevance of these two peptides as potential antileishmanial agents. In the case of L. major promastigotes, Melittin and Dermaseptin showed inhibitory activity, the latter also showed a selectivity index of 8 against intracellular forms. These findings suggest Andropin, Cecropin A and Dermaseptin as potential therapeutic tools to treat New and Old World cutaneous leishmaniasis. © 2011 Elsevier Inc.

Forero-Rodriguez J.,Fundacion Institute Inmunologia Of Colombia Fidic | Forero-Rodriguez J.,National University of Colombia | Garzon-Ospina D.,Fundacion Institute Inmunologia Of Colombia Fidic | Garzon-Ospina D.,El Rosario University | And 2 more authors.
Malaria Journal | Year: 2014

Background: Plasmodium vivax is one of the five species causing malaria in human beings, affecting around 391 million people annually. The development of an anti-malarial vaccine has been proposed as an alternative for controlling this disease. However, its development has been hampered by allele-specific responses produced by the high genetic diversity shown by some parasite antigens. Evaluating these antigens' genetic diversity is thus essential when designing a completely effective vaccine. Methods. The gene sequences of Plasmodium vivax p12 (pv12) and p38 (pv38), obtained from field isolates in Colombia, were used for evaluating haplotype polymorphism and distribution by population genetics analysis. The evolutionary forces generating the variation pattern so observed were also determined. Results: Both pv12 and pv38 were shown to have low genetic diversity. The neutral model for pv12 could not be discarded, whilst polymorphism in pv38 was maintained by balanced selection restricted to the gene's 5′ region. Both encoded proteins seemed to have functional/structural constraints due to the presence of s48/45 domains, which were seen to be highly conserved. Conclusions: Due to the role that malaria parasite P12 and P38 proteins seem to play during invasion in Plasmodium species, added to the Pv12 and Pv38 antigenic characteristics and the low genetic diversity observed, these proteins might be good candidates to be evaluated in the design of a multistage/multi-antigen vaccine. © 2014 Forero-Rodríguez et al.; licensee BioMed Central Ltd.

Patarroyo M.E.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.E.,National University of Colombia | Moreno-Vranich A.,Fundacion Institute Inmunologia Of Colombia Fidic | Bermudez A.,Fundacion Institute Inmunologia Of Colombia Fidic
Biochemical and Biophysical Research Communications | Year: 2012

Modified HABP (mHABP) regions interacting with HLA-DRβ1* molecules have a more restricted conformation and/or sequence than other mHABPs which do not fit perfectly into their peptide binding regions (PBR) and do not induce an acceptable immune response due to the critical role of their Φ and Ψ torsion angles. These angle's critical role was determined in such highly immunogenic, protection-inducing response against experimental malaria using the conformers (mHABPs) obtained by 1H-NMR and superimposed into HLA-DRβ1*-like Aotus monkey molecules; their phi (Φ) and psi (Ψ) angles were measured and the H-bond formation between these molecules was evaluated. The aforementioned mHABP propensity to assume a regular conformation similar to a left-handed polyproline type II helix (PPIIL) led to suggesting that favouring these conformations according to their amino acid sequence would lead to high antibody titre production and sterile protective immunity induction against malaria, thereby adding new principles or rules for vaccine development, malaria being one of them. © 2012 Elsevier Inc.

Moreno-Vranich A.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.E.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.E.,National University of Colombia
Biochemical and Biophysical Research Communications | Year: 2012

Conserved Plasmodium falciparum high activity binding peptides' (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides' steric-electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals' disposition, to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome. © 2012 Elsevier Inc.

Patarroyo M.E.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.E.,National University of Colombia | Bermudez A.,Fundacion Institute Inmunologia Of Colombia Fidic | Bermudez A.,El Rosario University | And 2 more authors.
Chemical Reviews | Year: 2011

Identifying the principles and rules for developing a logical, rational vaccine methodology against various diseases, is discussed. SPf66, the first multiantigenic, multistage, minimal subunit-based, chemically synthesized anti-P. falciparum malaria vaccine. A robust, sensitive, and specific methodology is developed for defining the intimate molecular interactions mediating merozoite invasion of RBC by synthesizing short merozoite-derived protein peptides binding specifically and with high affinity (HABP) to RBCs. Conserved HABP-mediated sporozoite binding to hepatic cells is identified in EBA-175 for developing a multiantigenic, multistage, fully protective antimalarial vaccine. for developing a logical and rational vaccine methodology at the molecular level, monkeys' immune system molecules is analyzed by cloning and sequencing the Aotus genes encoding immunoglobulins, cytokines, and Class I and II molecules.

Moreno-Perez D.A.,Fundacion Institute Inmunologia Of Colombia Fidic | Moreno-Perez D.A.,El Rosario University | Saldarriaga A.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.A.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.A.,El Rosario University
Malaria Journal | Year: 2013

Background: Plasmodium vivax continues to be the most widely distributed malarial parasite species in tropical and sub-tropical areas, causing high morbidity indices around the world. Better understanding of the proteins used by the parasite during the invasion of red blood cells is required to obtain an effective vaccine against this disease. This study describes characterizing the P. vivax asparagine-rich protein (PvARP) and examines its antigenicity in natural infection. Methods. The target gene in the study was selected according to a previous in silico analysis using profile hidden Markov models which identified P. vivax proteins that play a possible role in invasion. Transcription of the arp gene in the P. vivax VCG-1 strain was here evaluated by RT-PCR. Specific human antibodies against PvARP were used to confirm protein expression by Western blot as well as its subcellular localization by immunofluorescence. Recognition of recombinant PvARP by sera from P. vivax-infected individuals was evaluated by ELISA. Results: VCG-1 strain PvARP is a 281-residue-long molecule, which is encoded by a single exon and has an N-terminal secretion signal, as well as a tandem repeat region. This protein is expressed in mature schizonts and is located on the surface of merozoites, having an apparent accumulation towards their apical pole. Sera from P. vivax-infected patients recognized the recombinant, thereby suggesting that this protein is targeted by the immune response during infection. Conclusions: This study showed the characterization of PvARP and its antigenicity. Further assays orientated towards evaluating this antigen's functional importance during parasite invasion are being carried out. © 2013 Moreno-Pérez et al.; licensee BioMed Central Ltd.

Moreno-Perez D.A.,Fundacion Institute Inmunologia Of Colombia Fidic | Moreno-Perez D.A.,El Rosario University | Ruiz J.A.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.A.,Fundacion Institute Inmunologia Of Colombia Fidic | Patarroyo M.A.,El Rosario University
Biology of the Cell | Year: 2013

Reticulocytes represent the main invasion target for Plasmodium vivax, the second most prevalent parasite species around the world causing malaria in humans. In spite of these cells' importance in research into malaria, biological knowledge related to the nature of the host has been limited, given the technical difficulties present in working with them in the laboratory. Poor reticulocyte recovery from total blood, by different techniques, has hampered continuous in vitro P. vivax cultures being developed, thereby delaying basic investigation in this parasite species. Intense research during the last few years has led to advances being made in developing methodologies orientated towards obtaining enriched reticulocytes from differing sources, thereby providing invaluable information for developing new strategies aimed at preventing infection caused by malaria. This review describes the most recent studies related to obtaining reticulocytes and discusses approaches which could contribute towards knowledge regarding molecular interactions between target cell proteins and their main infective agent, P. vivax. © 2013 Société Française des Microscopies and Société de Biologie Cellulaire de France.

Vizcaino C.,Fundacion Institute Inmunologia Of Colombia Fidic
PLoS computational biology | Year: 2010

The mycobacterial cell envelope has been implicated in the pathogenicity of tuberculosis and therefore has been a prime target for the identification and characterization of surface proteins with potential application in drug and vaccine development. In this study, the genome of Mycobacterium tuberculosis H37Rv was screened using Machine Learning tools that included feature-based predictors, general localizers and transmembrane topology predictors to identify proteins that are potentially secreted to the surface of M. tuberculosis, or to the extracellular milieu through different secretory pathways. The subcellular localization of a set of 8 hypothetically secreted/surface candidate proteins was experimentally assessed by cellular fractionation and immunoelectron microscopy (IEM) to determine the reliability of the computational methodology proposed here, using 4 secreted/surface proteins with experimental confirmation as positive controls and 2 cytoplasmic proteins as negative controls. Subcellular fractionation and IEM studies provided evidence that the candidate proteins Rv0403c, Rv3630, Rv1022, Rv0835, Rv0361 and Rv0178 are secreted either to the mycobacterial surface or to the extracellular milieu. Surface localization was also confirmed for the positive controls, whereas negative controls were located on the cytoplasm. Based on statistical learning methods, we obtained computational subcellular localization predictions that were experimentally assessed and allowed us to construct a computational protocol with experimental support that allowed us to identify a new set of secreted/surface proteins as potential vaccine candidates.

Patarroyo M.A.,Fundacion Institute Inmunologia Of Colombia Fidic
Expert review of vaccines | Year: 2012

Malaria caused by Plasmodium vivax continues being a public health problem in tropical and subtropical areas throughout the whole world. In spite of this species' epidemiological importance, its biological complexity has hampered advances being made in the field of vaccine development. Few antigens have been described and analyzed to date in preclinical and clinical studies, thereby highlighting the great challenge facing groups currently working on this parasite species. This review summarizes the most representative work done during the last few years and discusses the approaches adopted in making progress towards an anti-Plasmodium vivax vaccine.

The scaling properties of density functionals are key for fundamentally understanding density functional theory. Accordingly, the dependence of density functionals on the number of particles is of paramount relevance. The numerical exploration by Rong et al. addressed N-scaling for a set of quantum information quantities; they found linear relationships between each one of them and the electronic population for atoms, molecules, and atoms in molecules. The main motivation for their computational work was that the theoretical scaling of these quantities is unknown; however, these scaling properties can be analytically determined. Here I reveal the derivation of the N-scaling rules for the quantities studied by Rong et al. by following the procedure introduced in Comput. Theor. Chem., 2015, 1053, 38. In addition, a new atomic scaling rule explains the linear relationship between atomic populations and atomic values of the same quantum information quantities. © 2015 the Owner Societies.

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