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Acceso Abierto

Diseño de una metodología in vitro para la evaluación de antígenos peptídicos candidatos a vacuna contra tuberculosis

dc.contributor.advisorOcampo Cifuentes, Marisol
dc.contributor.advisorPatarroyo Gutiérrez, Manuel Alfonso
dc.creatorCarabalí Isajar, Mary Lilián
dc.creator.degreeDoctor en Ciencias Biomédicas y Biológicas
dc.creator.degreeLevelDoctorado
dc.creator.degreetypeFull time
dc.date.accessioned2023-08-23T01:41:47Z
dc.date.available2023-08-23T01:41:47Z
dc.date.created2023-03-06
dc.descriptionPese a los esfuerzos mundiales por erradicar la tuberculosis, esta enfermedad persiste entre las primeras causas de muerte por un agente infeccioso a nivel mundial, aún por encima del VIH y superada sólo por el SARS COV-2, siendo la causa de muerte de 1,5 millones de personas en 2021. Lo anterior se suma a los crecientes casos de tuberculosis producto de cepas micobacterianas multirresistentes y extensivamente resistentes. La actual vacuna BCG, que es la única avalada por OMS, es ineficiente para conferir protección a la mayoría de la población frente a la forma más prevalente de la enfermedad. Mycobacterium tuberculosis es el principal agente causal de la tuberculosis y posee muchos mecanismos para evadir la respuesta inmune que despliega el hospedero como defensa frente a la infección; por tal razón, es preciso generar una vacuna que confiera una mejor respuesta a la actualmente obtenida con la BCG. Sin embargo, la falta de un modelo en donde se puedan evaluar los candidatos a vacuna y correlacionarlo con protección en humanos, ha sido una de las mayores limitantes en el desarrollo de dicha vacuna. De ahí que se están considerando los ensayos in vitro como una alternativa viable en esta tarea. Algunos de estos ensayos han permitido evidenciar la inhibición del crecimiento bacteriano intracelular, estudiándose tanto el efecto de la respuesta celular como de anticuerpos, citoquinas y quimioquinas efectoras involucradas en este proceso. Por otra parte, la Fundación Instituto de Inmunología de Colombia ha buscado antígenos candidatos para el diseño de una vacuna sintética antituberculosis, mediante una metodología robusta, lógica y racional, con la cual se han identificado péptidos derivados de proteínas de Mycobacterium tuberculosis que pueden estar involucrados en la interacción micobacteria-célula hospedera; no obstante, no se ha evaluado la inmunogenicidad de estos péptidos o de sus secuencias modificadas en cuanto al potencial protector contra Mycobacterium tuberculosis. Por lo tanto, el presente proyecto planteó realizar diferentes ensayos in vitro con células humanas, para evaluar la posible respuesta inmune protectora que pudieran conferir los péptidos candidatos a vacuna.
dc.description.abstractDespite global efforts to eradicate tuberculosis, this disease persists among the leading causes of death from an infectious agent worldwide, still above HIV and surpassed only by SARS COV-2, being the cause of death of 1, 5 million people in 2021. This is added to the increasing cases of tuberculosis caused by multiresistant and extensively resistant mycobacterial strains. The current BCG vaccine, which is the only one endorsed by the WHO, is inefficient in providing protection to the majority of the population against the most prevalent form of the disease. Mycobacterium tuberculosis is the main causative agent of tuberculosis and has many mechanisms to evade the immune response displayed by the host as a defense against infection; For this reason, it is necessary to generate a vaccine that confers a better response than that currently obtained with BCG. However, the lack of a model where vaccine candidates can be evaluated and correlated with protection in humans has been one of the greatest limitations in the development of said vaccine. Hence, in vitro tests are being considered as a viable alternative in this task. Some of these tests have made it possible to demonstrate the inhibition of intracellular bacterial growth, studying both the effect of the cellular response and of antibodies, cytokines and effector chemokines involved in this process. On the other hand, the Fundación Instituto de Inmunología de Colombia has searched for candidate antigens for the design of a synthetic anti-tuberculosis vaccine, using a robust, logical and rational methodology, with which peptides derived from Mycobacterium tuberculosis proteins that may be involved have been identified in the mycobacterium-host cell interaction; however, the immunogenicity of these peptides or their modified sequences for protective potential against Mycobacterium tuberculosis has not been evaluated. Therefore, the present project proposed carrying out different in vitro assays with human cells, to evaluate the possible protective immune response that the vaccine candidate peptides could confer.
dc.description.sponsorshipMinisterio de Ciencia, Tecnología e Innovación de Colombia (Minciencias) a través de Beca de Doctorado 647
dc.format.extent112 pp
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.48713/10336_40733
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/40733
dc.language.isospa
dc.publisherUniversidad del Rosario
dc.publisher.departmentEscuela de Medicina y Ciencias de la Salud
dc.publisher.programDoctorado en Ciencias Biomédicas y Biológicas
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)
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dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
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dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectMycobacterium tuberculosis
dc.subjectMtb
dc.subjectTuberculosis
dc.subjectVacuna
dc.subjectPéptido
dc.subjectProteínas
dc.subjectRespuesta inmune celular
dc.subjectRespuesta inmune humoral
dc.subjectLinfocitos
dc.subjectMacrófagos
dc.subjectNeutrófilos anticuerpos
dc.subjectCitoquinas
dc.subject.keywordMycobacterium tuberculosis
dc.subject.keywordMtb
dc.subject.keywordTuberculosis
dc.subject.keywordVaccine
dc.subject.keywordPeptide
dc.subject.keywordProteins
dc.subject.keywordCellular immune response
dc.subject.keywordHumoral immune response
dc.subject.keywordLymphocytes
dc.subject.keywordMacrophages
dc.subject.keywordNeutrophils
dc.subject.keywordAntibodies
dc.subject.keywordCytokines
dc.titleDiseño de una metodología in vitro para la evaluación de antígenos peptídicos candidatos a vacuna contra tuberculosis
dc.title.TranslatedTitleDesign of an in vitro methodology for the evaluation of candidate peptide antigens for a tuberculosis vaccine
dc.typemasterThesis
dc.type.documentTesis
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaTesis
local.department.reportEscuela de Medicina y Ciencias de la Salud
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