Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón

ilustraciones, diagramas, tablas

Autores:
Beltrán Castañeda, Jeimy Yurani
Tipo de recurso:
Fecha de publicación:
2024
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/86730
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/86730
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología::571 - Fisiología y temas relacionados
570 - Biología::576 - Genética y evolución
INMUNORRESPUESTA
MICROBIOLOGIA-TECNICA
HISTOCOMPATIBILIDAD
ANTIGENOS DE HISTOCOMPATIBILIDAD
Immune response
Microbiology-technique
Histocompatibility
Histocompatibility antigens
Selección natural
Péptidos quiméricos
Plasmodium yoelii
Epítopos T
Epítopos B
Inmunogenicidad
Antigenicidad
Natural selection
T epitopes
B epitopes
Chimeric peptides
Immunogenicity
Antigenicity
Rights
openAccess
License
Reconocimiento 4.0 Internacional
id UNACIONAL2_74b1b5b11447ff3f91f292567c410b14
oai_identifier_str oai:repositorio.unal.edu.co:unal/86730
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
dc.title.translated.eng.fl_str_mv Evaluation of the protective immune response stimulated by B epitopes derived from the Plasmodium yoelii MSP-1 protein optimized for binding to mouse major histocompatibility complex class II molecules
title Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
spellingShingle Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
570 - Biología::571 - Fisiología y temas relacionados
570 - Biología::576 - Genética y evolución
INMUNORRESPUESTA
MICROBIOLOGIA-TECNICA
HISTOCOMPATIBILIDAD
ANTIGENOS DE HISTOCOMPATIBILIDAD
Immune response
Microbiology-technique
Histocompatibility
Histocompatibility antigens
Selección natural
Péptidos quiméricos
Plasmodium yoelii
Epítopos T
Epítopos B
Inmunogenicidad
Antigenicidad
Natural selection
T epitopes
B epitopes
Chimeric peptides
Immunogenicity
Antigenicity
title_short Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
title_full Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
title_fullStr Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
title_full_unstemmed Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
title_sort Evaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratón
dc.creator.fl_str_mv Beltrán Castañeda, Jeimy Yurani
dc.contributor.advisor.spa.fl_str_mv Díaz Arévalo, Diana
Patarroyo Gutiérrez, Manuel Alfonso
dc.contributor.author.spa.fl_str_mv Beltrán Castañeda, Jeimy Yurani
dc.contributor.educationalvalidator.spa.fl_str_mv Rodríguez Obediente, Kewin Jair
dc.subject.ddc.spa.fl_str_mv 570 - Biología::571 - Fisiología y temas relacionados
570 - Biología::576 - Genética y evolución
topic 570 - Biología::571 - Fisiología y temas relacionados
570 - Biología::576 - Genética y evolución
INMUNORRESPUESTA
MICROBIOLOGIA-TECNICA
HISTOCOMPATIBILIDAD
ANTIGENOS DE HISTOCOMPATIBILIDAD
Immune response
Microbiology-technique
Histocompatibility
Histocompatibility antigens
Selección natural
Péptidos quiméricos
Plasmodium yoelii
Epítopos T
Epítopos B
Inmunogenicidad
Antigenicidad
Natural selection
T epitopes
B epitopes
Chimeric peptides
Immunogenicity
Antigenicity
dc.subject.lemb.spa.fl_str_mv INMUNORRESPUESTA
MICROBIOLOGIA-TECNICA
HISTOCOMPATIBILIDAD
ANTIGENOS DE HISTOCOMPATIBILIDAD
dc.subject.lemb.eng.fl_str_mv Immune response
Microbiology-technique
Histocompatibility
Histocompatibility antigens
dc.subject.proposal.spa.fl_str_mv Selección natural
Péptidos quiméricos
Plasmodium yoelii
Epítopos T
Epítopos B
Inmunogenicidad
Antigenicidad
dc.subject.proposal.eng.fl_str_mv Natural selection
T epitopes
B epitopes
Chimeric peptides
Immunogenicity
Antigenicity
description ilustraciones, diagramas, tablas
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-08-15T19:53:15Z
dc.date.available.none.fl_str_mv 2024-08-15T19:53:15Z
dc.date.issued.none.fl_str_mv 2024
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/86730
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/86730
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
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dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv Reconocimiento 4.0 Internacional
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dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Reconocimiento 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
http://purl.org/coar/access_right/c_abf2
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dc.format.extent.spa.fl_str_mv 68 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv Bogotá - Ciencias - Maestría en Ciencias - Microbiología
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
institution Universidad Nacional de Colombia
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spelling Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Díaz Arévalo, Diana4b9a1ebb1633a8c2defe6148569778fcPatarroyo Gutiérrez, Manuel Alfonso30322a85ae0ad9c1368bae791386bffeBeltrán Castañeda, Jeimy Yurani2ef02487fc0ed9be1f8e41c4a4777d4bRodríguez Obediente, Kewin Jair2024-08-15T19:53:15Z2024-08-15T19:53:15Z2024https://repositorio.unal.edu.co/handle/unal/86730Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramas, tablasEl modelo de malaria murina ha sido ampliamente usado en ensayos preliminares de protección con aquellas proteínas de Plasmodium yoelii que son homólogas a las proteínas de P. vivax, al evaluar posibles candidatos a vacuna. La proteína MSP1 es la proteína más abundante localizada en la superficie del merozoíto y está involucrada en la unión inicial a la membrana del glóbulo rojo durante el proceso de invasión a eritrocitos. En el presente estudio, como prueba de concepto, se caracterizó la respuesta inmune protectiva de epítopos B de la proteína PyMSP1-42 kDa con un epítopo T artificial para la unión a H2-IEd, utilizando ratones BALB/c. Se seleccionaron epítopos B bajo un análisis de restricción funcional in silico, encontrando dos regiones conservadas que pertenecen al fragmento 33 kDa y 19 kDa; con base en este análisis, se sintetizaron dieciséis péptidos cubriendo la totalidad de las regiones conservadas y, en ensayos in vitro, se identificaron 3 péptidos con capacidad de unión a eritrocitos, capacidad de inhibición de la invasión y con capacidad antigénica. Mediante análisis bioinformáticos, se realizó la optimización de los epítopos B seleccionados, a través de la articulación de un epítopo T artificial y se evaluó su unión in vitro a moléculas H2-IEd. Los péptidos quiméricos 43758 y 43762 mostraron perfiles de unión superior al 50% a la molécula del Complejo Mayor de Histocompatibilidad (MHC, del inglés Major Histocompatibility Complex) de clase II murino, además de un perfil de isotipos IgG1 e IgG2 y una respuesta mediada por TNFα, como posible mediador de la eliminación del parásito durante la infección temprana de P. yoelii. Este trabajo propone una metodología racional y robusta para la optimización de péptidos conservados a través de constructos articulados de epítopos B, y epítopos T completamente artificiales, como una estrategia novedosa para el diseño de candidatos peptídicos inmunoprofilácticos para el desarrollo de una vacuna sintética multiepítopo - multiantígeno – multiestadio contra la malaria (Texto tomado de la fuente).The murine malaria model has been widely used in preliminary protection trials with Plasmodium yoelii proteins that are homologous to P. vivax proteins as potential vaccine candidates. The MSP1 protein is the most abundant protein located on the surface of the merozoite and is involved in the initial binding to the red blood cell membrane during the invasion process to erythrocytes. In the present study, as a proof of concept, the protective immune response of B epitopes of PyMSP1-42 kDa protein with an artificial T epitope for H2-IEd binding was characterized using BALB/c mice. B epitopes under functional restriction analysis were selected in silico, two conserved regions belonging to the 33 kDa and 19 kDa fragments were found; sixteen peptides covering the conserved regions were synthesized, 3 of them displaying erythrocyte binding ability, invasion inhibition ability and antigenicity. The selected B epitopes were then optimized through bioinformatics analysis, articulating them with an artificial T epitope, and their in vitro binding to H2-IEd molecules was evaluated. Chimeric peptides 43758 and 43762 showed binding profiles greater than 50% to the murine MHC class II molecule; furthermore, they induced IgG1 and IgG2 isotype profiles and a TNFα-mediated response as a possible mediator of parasite clearance during early P. yoelii infection. This work proposes a robust and rational methodology to optimize conserved peptides by joining natural B epitopes with artificial T ones, as a novel strategy for designing immunoprophylactic peptide candidates in the development of a multiepitope – multiantigen – multistage malaria vaccine.MaestríaMagister en Ciencias – MicrobiologíaEl polimorfismo del gen msp1 fragmento 42 kDa se evaluó a partir de los datos de secuencias de P. yoelii y especies relacionadas filogenéticamente / tropismo por la célula hospedera (Tabla 2), obtenidos de la plataforma NCBI (https://www.ncbi.nlm.nih.gov). El servidor web TraslatorX (http://translatorx.co.uk/) (45), se utilizó para realizar un alineamiento múltiple conservando el ORF (del inglés, Open Reading Frame) para la proteína PyMSP1-42 kDa. El algoritmo GARD (Genetic Algorithm for Recombination Detection) se utilizó para detectar procesos de recombinación. Luego, los modelos IFEL (Internal Fixed Effects Likelihood), 24 SLAC (Single-Likelihood Ancestor Counting), FEL (Fixed Effects Likelihood), REL (Random Effects Likelihood) (46), MEME (Mixed Effects Model of Evolution) (47) y FUBAR (Fast, Unconstrained Bayesian Approximation) (48), se utilizaron para evaluar dinámicas de selección natural, integrando enfoques bayesianos o de máxima verosimilitud. Lo anterior con el objetivo de inferir codones bajo selección purificante (característica importante para predecir regiones mínimas funcionales). La ventana deslizante para inferir la tasa de divergencia genética (ω), se obtuvo en el software DnaSP6 (49). Las señales de selección natural intra-especie se evaluaron a través del método modificado de Nei-Gojobori, calculando la variación entre las tasas de sustitución no sinónima y sinónima (dN/dS). Además, se aplicó la corrección de Jukes-Cantor (50) para evaluar fenómenos inter-especie, teniendo en cuenta la diferencia entre las tasas de divergencia no sinónimas y sinónimas (KNKS). Aquellas regiones que presentaron valor ω > 1 se consideraron bajo selección purificante (51).Inmunología Celular y Molecular68 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - MicrobiologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::571 - Fisiología y temas relacionados570 - Biología::576 - Genética y evoluciónINMUNORRESPUESTAMICROBIOLOGIA-TECNICAHISTOCOMPATIBILIDADANTIGENOS DE HISTOCOMPATIBILIDADImmune responseMicrobiology-techniqueHistocompatibilityHistocompatibility antigensSelección naturalPéptidos quiméricosPlasmodium yoeliiEpítopos TEpítopos BInmunogenicidadAntigenicidadNatural selectionT epitopesB epitopesChimeric peptidesImmunogenicityAntigenicityEvaluación de la respuesta inmune protectiva estimulada por epítopes B derivados de la proteína MSP-1 de Plasmodium yoelii optimizados para la unión a moléculas del complejo mayor de histocompatibilidad de clase II de ratónEvaluation of the protective immune response stimulated by B epitopes derived from the Plasmodium yoelii MSP-1 protein optimized for binding to mouse major histocompatibility complex class II moleculesTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TM1. 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Infection and immunity. 2008;76(7):3312-20.InvestigadoresLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86730/3/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD53ORIGINALTesis Jeimy Beltran -15-08-24 Repositorio.pdfTesis Jeimy Beltran -15-08-24 Repositorio.pdfTesis de Maestría en Ciencias – Microbiologíaapplication/pdf2282713https://repositorio.unal.edu.co/bitstream/unal/86730/4/Tesis%20Jeimy%20Beltran%20-15-08-24%20Repositorio.pdfe095e480f27b3a6c5b092a6d0da06d42MD54THUMBNAILTesis Jeimy Beltran -15-08-24 Repositorio.pdf.jpgTesis Jeimy Beltran -15-08-24 Repositorio.pdf.jpgGenerated Thumbnailimage/jpeg5112https://repositorio.unal.edu.co/bitstream/unal/86730/5/Tesis%20Jeimy%20Beltran%20-15-08-24%20Repositorio.pdf.jpg989fcb0a89ef33a95432cbd68b1e941eMD55unal/86730oai:repositorio.unal.edu.co:unal/867302024-08-15 23:06:23.396Repositorio Institucional Universidad Nacional de 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