Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia
ilustraciones a color, diagramas, fotografías
- Autores:
-
Melo Velanida, Fredy Leonardo
- Tipo de recurso:
- Fecha de publicación:
- 2023
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/85352
- Palabra clave:
- 610 - Medicina y salud::615 - Farmacología y terapéutica
610 - Medicina y salud::616 - Enfermedades
Simulación del acoplamiento molecular
Plasmodium falciparum
Plasmodium berghei
Antígenos de protozoos
Plasmodium yoelii
Malaria-Tratamiento farmacológico
Técnicas Inmunológicas
Molecular docking simulation
Antigens, protozoan
Immunologic techniques
Proteína MSP1
Plasmodium falciparum 3D7
Plasmodium berghei ANKA
Plasmodium yoelii 17XL
Malaria
Modificación amida reducida
Acoplamiento molecular
MSP1 protein
Reduced amide modification
Molecular docking
- Rights
- openAccess
- License
- Atribución-NoComercial-CompartirIgual 4.0 Internacional
| id |
UNACIONAL2_9946efe57ddb5c8c0e47e401f5feafbf |
|---|---|
| oai_identifier_str |
oai:repositorio.unal.edu.co:unal/85352 |
| network_acronym_str |
UNACIONAL2 |
| network_name_str |
Universidad Nacional de Colombia |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| dc.title.translated.eng.fl_str_mv |
Exploration of structural modifications of an MSP1 protein antigen from Plasmodium spp and their influence on its molecular recognition property by murine and human sera from people from post-conflict areas in Colombia |
| title |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| spellingShingle |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia 610 - Medicina y salud::615 - Farmacología y terapéutica 610 - Medicina y salud::616 - Enfermedades Simulación del acoplamiento molecular Plasmodium falciparum Plasmodium berghei Antígenos de protozoos Plasmodium yoelii Malaria-Tratamiento farmacológico Técnicas Inmunológicas Molecular docking simulation Antigens, protozoan Immunologic techniques Proteína MSP1 Plasmodium falciparum 3D7 Plasmodium berghei ANKA Plasmodium yoelii 17XL Malaria Modificación amida reducida Acoplamiento molecular MSP1 protein Reduced amide modification Molecular docking |
| title_short |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| title_full |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| title_fullStr |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| title_full_unstemmed |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| title_sort |
Exploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en Colombia |
| dc.creator.fl_str_mv |
Melo Velanida, Fredy Leonardo |
| dc.contributor.advisor.spa.fl_str_mv |
Lozano Moreno, José Manuel |
| dc.contributor.author.spa.fl_str_mv |
Melo Velanida, Fredy Leonardo |
| dc.contributor.researchgroup.spa.fl_str_mv |
Mimetismo Molecular de Los Agentes Infecciosos |
| dc.subject.ddc.spa.fl_str_mv |
610 - Medicina y salud::615 - Farmacología y terapéutica 610 - Medicina y salud::616 - Enfermedades |
| topic |
610 - Medicina y salud::615 - Farmacología y terapéutica 610 - Medicina y salud::616 - Enfermedades Simulación del acoplamiento molecular Plasmodium falciparum Plasmodium berghei Antígenos de protozoos Plasmodium yoelii Malaria-Tratamiento farmacológico Técnicas Inmunológicas Molecular docking simulation Antigens, protozoan Immunologic techniques Proteína MSP1 Plasmodium falciparum 3D7 Plasmodium berghei ANKA Plasmodium yoelii 17XL Malaria Modificación amida reducida Acoplamiento molecular MSP1 protein Reduced amide modification Molecular docking |
| dc.subject.decs.spa.fl_str_mv |
Simulación del acoplamiento molecular Plasmodium falciparum Plasmodium berghei Antígenos de protozoos Plasmodium yoelii Malaria-Tratamiento farmacológico Técnicas Inmunológicas |
| dc.subject.decs.eng.fl_str_mv |
Molecular docking simulation Antigens, protozoan Immunologic techniques |
| dc.subject.proposal.spa.fl_str_mv |
Proteína MSP1 Plasmodium falciparum 3D7 Plasmodium berghei ANKA Plasmodium yoelii 17XL Malaria Modificación amida reducida Acoplamiento molecular |
| dc.subject.proposal.eng.fl_str_mv |
MSP1 protein Reduced amide modification Molecular docking |
| description |
ilustraciones a color, diagramas, fotografías |
| publishDate |
2023 |
| dc.date.issued.none.fl_str_mv |
2023-11-07 |
| dc.date.accessioned.none.fl_str_mv |
2024-01-17T18:32:49Z |
| dc.date.available.none.fl_str_mv |
2024-01-17T18:32:49Z |
| 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/85352 |
| 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/85352 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 |
| dc.relation.references.spa.fl_str_mv |
Abbas, A. K., Lichtman, A. H., & Pillai, S. (2015). Student Consult (8°; Elsevier, ed.). https://doi.org/10.1016/j.genhosppsych.2013.05.007 Acosta, C., Galindo, C., Schellenberg, D., Aponte, J., Kahigwa, E., Urassa, H., … Alonso, P. (1999). Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. Tropical Medicine and International Health, 4(5), 368–376. https://doi.org/10.1046/j.1365-3156.1999.00406. Aikawa M, Miller LH, Johnson J, Rabbege J (1978) Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. J. Cell Biol. 77: 72–82. Akter, J., Khoury, D. S., Aogo, R., Lansink, L. I., SheelaNair, A., Thomas, B. S., … Haque, A. (2019). Plasmodium-specific antibodies block in vivo parasite growth without clearing infected red blood cells. PLoS Pathogens, 15(2), 1–24. https://doi.org/10.1371/journal.ppat.1007599 Al-Yaman, F., Genton, B., Anders, R., Falk, M., Triglia, T., Lewis, D., … Alpers, M. (1994). Relationship between humoral response to Plasmodium falciparum merozoite surface antigen- 2 and malaria morbidity in a highly endemic area of Papua New Guinea. American Journal of Tropical Medicine and Hygiene, 51, 593–602. https://doi.org/10.4269/ajtmh.1994.51.593 Angulo, I., & Fresno, M. (2002, November). Cytokines in the pathogenesis of and protection against malaria. Clinical and Diagnostic Laboratory Immunology, Vol. 9, pp. 1145–1152. https://doi.org/10.1128/CDLI.9.6.1145-1152.2002 Arias-Murillo, Y., Osorio-Arango, K., Bayona, B., Ercilla, Guadalupe., Beltrán-Durán, Mauricio. (2017). Determinación del polimorfismo de HLA-A, -B y -DRB1 en donantes de órganos con muerte encefálica representativos de la población general colombiana, 2007-2014. Biomédica, 37, 184-190. doi: http://dx.doi.org/10.7705/biomedica.v37i2.3263 Arlett, H., & Spielmann, T. (2014). Preparation of Parasite Protein Extracts and Western Blot Analysis.In Bio-protocol LLC (Vol. 4). Arnaiz-Villena, A., Muñiz, E., del Palacio-Gruber, J., Campos, C., Alonso-Rubio, J., Gomez-Casado, E., … Silvera, C. (2016). Ancestry of Amerindians and its Impact in Anthropology, Transplantation, HLA Pharmacogenomics and Epidemiology by HLA Study in Wiwa Colombian Population. Open Medicine Journal, 3(1), 269–285. https://doi.org/10.2174/1874220301603010269 Arrunategui, A. M., Villegas, A., Ocampo, L. Á., Rodríguez, L. M., & Badih, A. (2013). Frecuencias alélicas, genotípicas y haplotípicas del sistema HLA clase I y II en donantes de una población del suroccidente colombiano. Acta Medica Colombiana, 38(1), 16–21. Aurrecoechea, C., Brestelli, J., Brunk, B., Dommer, J., Fischer, S., Gajria, B., … Wang, H. (2009). PlasmoDB: A functional genomic database for malaria parasites. Nucleic Acids Research, 37(SUPPL. 1), D539. https://doi.org/10.1093/nar/gkn814 Ávila-Portillo, L. M., Carmona, A., Franco, L., Briceño, I., Casas, M. C., & Gómez, A. (2010). Bajo polimorfismo en el sistema de antígenos de leucocitos humanos en población mestiza colombiana. Universitas Médica, 51(4), 359–370. https://doi.org/10.11144/javeriana.umed51- 4.bpsa Bahl, A., Brunk, B., Crabtree, J., Fraunholz, M., Gajria, B., Grant, G., … Whetzel, P. (2003). PlasmoDB: The Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Research, 31(1), 212–215. https://doi.org/10.1093/nar/gkg081 Baird, J. (1998). Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum. Annals of Tropical Medicine and Parasitology, 92(4), 367–390. https://doi.org/10.1080/00034989859366 Bannister, L., Hopkins, J., Fowler, R., Krishna, S., & Mitchell, G. (2000). A Brief Illustrated Guide to the Ultrastructure of Plasmodium falciparum Asexual Blood Stages. Parásitology Today, 16(10), 427–433. https://doi.org/10.1016/S0169-4758(00)01755-5 Bastian, M., Lozano, J. M., Patarroyo, M. E., Pluschke, G., & Daubenberger, C. A. (2004). Characterization of a reduced peptide bond analogue of a promiscuous CD4 T cell epitope derived from the Plasmodium falciparum malaria vaccine candidate merozoite surface protein 1. Molecular Immunology, 41, 775–784. https://doi.org/10.1016/j.molimm.2004.04.019 Batista-Duharte, A., Lastre, M., & Pérez, O. (2014). Adyuvantes inmunológicos. Determinantes en el balance eficacia-toxicidad de las vacunas contemporáneas. Enfermedades Infecciosas y Microbiologia Clinica, 32(2), 106–114. https://doi.org/10.1016/j.eimc.2012.11.012 Battle, K., Karhunen, M., Bhatt, S., Gething, P., Howes, R., Golding, N., … Hay, S. (2014). Geographical variation in Plasmodium vivax relapse. Malaria Journal, 13(1), 1–16. https://doi.org/10.1186/1475-2875-13-144 Beeson, J., Drew, D., Boyle, M., Feng, G., Fowkes, F., & Richards, J. (2016). Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria. FEMS Microbiology Reviews, 40(3), 343–372. https://doi.org/10.1093/femsre/fuw001 Bergmann-Leitner, E., Duncan, E., & Angov, E. (2012). Malaria Vaccine. In O. Okwa (Ed.), The Impact of Immune Responses on the Asexual Erythrocytic Stages of Plasmodium and the Implication for Vaccine Development. https://doi.org/10.5772/33130 Bermeo, S., Guerra, M. T., & Ostos Alfonso, H. (2010). Vista de Frecuencias de HLA-A, B y DRB1 en una población de Huila-Colombia. Revista Facultad de Salud, 2(1), 9–19. Bernal, J., & Briceño, I. (2013). Estudios de HLA en Colombia. Acta Medica Colombiana, Vol. 38, pp.5–6. Vol. 38, pp.5–6. P. (1986). Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion. Proceedings of the National Academy of Sciences of the United States of America, 83(4), 1065– 1069. https://doi.org/10.1073/pnas.83.4.1065 Birkett, A. (2016). Status of vaccine research and development of vaccines for malaria. Vaccine, 34, 2915–2920. https://doi.org/10.1016/j.vaccine.2016.02.074 Black, C. G., Wang, L., Wu, T., & Coppel, R. L. (2003). Apical location of a novel EGF-like domain- containing protein of Plasmodium falciparum. Molecular and Biochemical Parasitology, 127(1),59–68. https://doi.org/10.1016/S0166-6851(02)00308-0 Black, C. G., Wu, T., Wang, L., Hibbs, A. R., & Coppel, R. L. (2001). Merozoite surface protein 8 of Plasmodium falciparum contains two epidermal growth factor-like domains. Molecular and Biochemical Parasitology, 114(2), 217–226. https://doi.org/10.1016/S0166-6851(01)00265-1 Blackman, M. J., Heidrich, H. G., Donachie, S., McBride, J. S., & Holder, A. (1990). A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. Journal of Experimental Medicine, 172, 379–382. https://doi.org/10.1084/jem.172.1.379 Blackman, M. J., Whittle, H., & Holder, A. (1991). Processing of the Plasmodium falciparum major merozoite surface protein-1: identification of a 33-kilodalton secondary processing product which is shed prior to erythrocyte invasion. Molecular and Biochemical Parasitology, 49, 35–44. https://doi.org/10.1016/0166-6851(91)90128-S Blasco, B., Leroy, Di., & Fidock, D. A. (2017). Antimalarial drug resistance: Linking Plasmodium falciparum parasite biology to the clinic. Nature Medicine, 23(8), 917–928. https://doi.org/10.1038/nm.4381 Bohley, P., & Seglen, P. (1992). Proteases and proteolysis in the lysosome. Experientia, 48(2), 151– 157. https://doi.org/10.1007/BF01923508 Bonanni, P. (1999). Demographic impact of vaccination: A review. Vaccine, 17(SUPPL. 3), 120–125. https://doi.org/10.1016/S0264-410X(99)00306-0 Boyle, M. J., Langer, C., Chan, J. A., Hodder, A., Coppel, R. L., Anders, R., & Beeson, J. (2014). Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum. Infection and Immunity, 82(3), 924–936. https://doi.org/10.1128/IAI.00866-13 Cai, Q., Peng, G., Bu, L., Lin, Y., Zhang, L., Lustigmen, S., & Wang, H. (2007). Immunogenicity and in vitro protective efficacy of a polyepitope Plasmodium falciparum candidate vaccine constructed by epitope shuffling. Vaccine, 25(28), 5155–5165. https://doi.org/10.1016/j.vaccine.2007.04.085 Camus, D., & Hadley, T. J. (1985). A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science, 230(4725), 553–556. https://doi.org/10.1126/science.3901257 Cavanagh, D. R., & McBride, J. S. (1997). Antigenicity of recombinant proteins derived from Plasmodium falciparum merozoite surface protein 1. Molecular and Biochemical Parasitology, 85(2), 197–211. https://doi.org/10.1016/S0166-6851(96)02826-5 Céspedes, N., Arévalo-Herrera, M., Felger, I., Reed, S., Kajava, A. V, Corradin, G., & Herrera, S. (2013). Antigenicity and immunogenicity of a novel chimeric peptide antigen based on the P. vivax circumsporozoite protein. Vaccine, 31, 4923–4930. https://doi.org/10.1016/j.vaccine.2013.05.082 Chaves, F., Calvo, J., Carvajal, C., Rivera, Z., Ramírez, L., Pinto, M., … Patarroyo, M. E. (2001). Synthesis, isolation and characterization of Plasmodium falciparum antigenic tetrabranched peptide dendrimers obtained by thiazolidine linkages. Journal of Peptide Research, 58(4), 307– 316. https://doi.org/10.1034/j.1399-3011.2001.00921. Chen, J. S., Liu, H., Yang, J., & Chou, K. (2007). Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids, 33, 423–428. https://doi.org/10.1007/s00726-006-0485-9 Christopher, A., MacRaild, C. A., Reiling, L., Wycherley, K., Boyle, M. J., Kienzle, V., … Anders, R. (2012). Antigenic characterization of an intrinsically unstructured protein, Plasmodium falciparum merozoite surface protein 2. Infection and Immunity, 80(12), 4177–4185. https://doi.org/10.1128/IAI.00665-12 Coffman, R. L., Sher, A., & Seder, R. A. (2010). Vaccine adjuvants: Putting innate immunity to work.Immunity, 33, 492–503. https://doi.org/10.1016/j.immuni.2010.10.002 Cohen, S. (1961). Gamma-Globulin and acquired immunity to human malaria. Nature, 192. Coligan, J. E., Bierer, B. E., David, M., Shevach, E., & Strober, W. (2007). Current Protocols in Immunology (Richard Coico, Ed.). https://doi.org/10.1002/0471142735 Collins, C. R., & Blackman, M. J. (2011). Apicomplexan AMA1 in Host Cell Invasion: A Model at the Junction? Cell Host & Microbe, 10(6), 531–533. https://doi.org/10.1016/J.CHOM.2011.11.006 Coppi, A., Natarajan, R., Pradel, G., Bennett, B. L., James, E. R., Roggero, M. A., … Sinnis, P. (2011). The malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host. Journal of Experimental Medicine, 208(2), 341–356. https://doi.org/10.1084/jem.20101488 Coppi, A., Pinzon-Ortiz, C., Hutter, C., & Sinnis, P. (2005). The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion. Journal of Experimental Medicine, 201(1), 27– 33. https://doi.org/10.1084/jem.20040989 Corman, V., Müller, M., Costabel, U., Timm, J., Binger, T., Meyer, B., … Drosten, C. (2012). Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillance, 17(49), 20334. https://doi.org/10.2807/ese.17.49.20334 Correa, P., Whitworth, W., Kuffner, T., McNicholl, J., & Anaya, J. (2002). HLA-DR and DQB1 gene polymorphism in the North-western Colombian population. Tissue Antigens, 59(5), 436–439. https://doi.org/10.1034/j.1399-0039.2002.590515 Cowman, A., Healer, J., Marapana, D., & Marsh, K. (2016, October 20). Malaria: Biology and Disease.Cell, Vol. 167, pp. 610–624. https://doi.org/10.1016/j.cell.2016.07.055 Cox, F. (2002, October). History of human parasitology. Clinical Microbiology Reviews, Vol. 15, pp.595–612. https://doi.org/10.1128/CMR.15.4.595-612.2002 Crewther, PE., Culvenor, J., Silva, A., Cooper, JA., Anders. RF. (1990). Plasmodium falciparum: two antigens of similar size are located in different compartments of the rhoptry. Exp. Parasitol. 70:193–206 Croft, N. P., & Purcell, A. W. (2011). Peptidomimetics: Modifying peptides in the pursuit of better vaccines. Expert Review of Vaccines, 10(2), 211–226. https://doi.org/10.1586/erv.10.161 Crompton, P. D., Kayala, M. A., Traore, B., Kayentao, K., Ongoiba, A., Weiss, G. E., … Pierce, S. K. (2010). A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proceedings of the National Academy of Sciences of the United States of America, 107(15), 6958–6963. https://doi.org/10.1073/pnas.1001323107 Cubillos, M., Espejo, F., Purmova, J., Martinez, J. C., & Patarroyo, M. E. (2003). Alpha helix shortening in 1522 MSP-1 conserved peptide analogs is associated with immunogenicity and protection against P. falciparum malaria. Proteins: Structure, Function and Genetics, 50(3), 400–409. https://doi.org/10.1002/prot.10314 Cuesta Astroz, Yesid, & Segura Latorre, Cesar. (2012). Métodos proteómicos aplicados al estudio de la malaria: Plasmodium falciparum. Acta Biológica Colombiana, 17(3), 463-484. Retrieved January 18, 2022, from http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120- 548X2012000300002&lng=en&tlng=es Culvenor, J., Day, K., & Anders, R. (1991). Plasmodium falciparum ring-infected erythrocyte surface antigen is released from merozoite dense granules after erythrocyte invasion. Infection and Immunity, 59(3), 1183–1187. https://doi.org/10.1128/iai.59.3.1183-1187.1991 D’Alessandro, U., Leach, A., Drakeley, C., Bennett, S., Olaleye, B., Fegan, G., … Targett, G. (1995). Efficacy trial of malaria vaccine SPf66 in Gambian infants. Lancet, 346(8973), 462–467. https://doi.org/10.1016/s0140-6736(95)91321-1 D’Amelio, E., Salemi, S., & D’Amelio, R. (2015, May 3). Anti-Infectious Human Vaccination in Historical Perspective. International Reviews of Immunology, Vol. 35, pp. 260–290. https://doi.org/10.3109/08830185.2015.1082177 Daubenberger, C. A., Nickel, B., Ciatto, C., Grütter, M. G., Pöltl‐Frank, F., Rossi, L., … Pluschke, G. (2002). Amino acid dimorphism and parasite immune evasion: cellular immune responses to a promiscuous epitope of Plasmodium falciparum merozoite surface protein 1 displaying dimorphic amino acid polymorphism are highly constrained. European Journal of Immunology, 32(12), 3667–3677. https://doi.org/10.1002/1521-4141(200212)32:12<3667::AID- IMMU3667>3.0.CO;2-C Davies, E. E. (1974). Ultrastructural studies on the early ookinete stage of Plasmodium berghei nigeriensis and its transformation into an oocyst. Annals of Tropical Medicine and Parasitology, 68(3), 283–290. https://doi.org/10.1080/00034983.1974.11686950 De Groot, A. S. (2006, March). Immunomics: Discovering new targets for vaccines and therapeutics. Drug Discovery Today, Vol. 11, pp. 203–209. https://doi.org/10.1016/S1359-6446(05)03720-7 De Sousa, K., & Doolan, D. (2016). Immunomics: a 21st century approach to vaccine development for complex pathogens. Parasitology, 143(Special issue), 236–244. https://doi.org/10.1017/S0031182015001079 Deans, J., Knight, A., Jean, W., Waters, A., Cohen, S., & Mitchell, G. (1988). Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen. Parasite Immunology, 10(5), 535–552. https://doi.org/10.1111/j.1365-3024.1988.tb00241 Dearsly, A., Sinden, R., & Self, I. (1990). Sexual development in malarial parasites: Gametocyte production, fertility and infectivity to the mosquito vector. Parasitology, 100(3), 359–368. https://doi.org/10.1017/S0031182000078628 Del Río-Ospina, L., Camargo, M., Soto-De León, S.C., Robayo-Calderón, K.L., Garzón-Ospina, D… (2019). Using next-generation sequencing for characterising HLA-DRB1 and DQB1 loci in a cohort of Colombian women. HLA Immnune Response Genetics, (94)5, 425-434. https://doi.org/10.1111/tan.13672 Dhanda, S. K., Gupta, S., Vir, P., & Raghava, G. (2013). Prediction of IL4 Inducing Peptides. Clinical and Developmental Immunology, 2013, 1–9. https://doi.org/10.1155/2013/263952 Dhanda, S. K., Vir, P., & Raghava, G. (2013). Designing of interferon-gamma inducing MHC class-II binders. Biology Direct, 8(1), 1–15. https://doi.org/10.1186/1745-6150-8-30 Dieng, M. M., Diawara, A., Manikandan, V., Tamim El Jarkass, H., Sermé, S. S., Sombié, S., Idaghdour, Y. (2020). Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria. Nature Communications, 11(1), 1–11. https://doi.org/10.1038/s41467- 020-18915-6 Dinko, B., & Pradel, G. (2016). Immune Evasion by Plasmodium falciparum Parasites: Converting a Host Protection Mechanism for the Parasite’s Benefit. Advances in Infectious Diseases, 06, 82– 95. https://doi.org/10.4236/aid.2016.62011 Dobaño, C., Sanz, H., Sorgho, H., Dosoo, D., Mpina, M., Ubillos, I., … Gyan, B. (2019). Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/ AS01E malaria vaccine efficacy. Nature Communications, 10(2174), 1–13. https://doi.org/10.1038/s41467-019-10195-z Donahue, CG., Carruthers, v., Gilk, sd., Ward, GE. (2000). The Toxoplasma homolog of Plasmodium apical membrane antigen-1 (AMA-1) is a microneme protein secreted in response to elevated intracellular calcium levels. Mol. Biochem. Parasitol. 111:15–30 Doolan, D. (Ed.). (2002). Malaria Methods and Protocols. New Jersey: Humana Press. Doolan, D., Dobaño, C., & Baird, J. (2009). Acquired immunity to Malaria. Clinical Microbiology Reviews, 22(1), 13–36. https://doi.org/10.1128/CMR.00025-08 Drakeley, C., Corran, P., Coleman, P., Tongren, J., McDonald, S. L., Carneiro, I., … Riley, E. (2005). Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure. Proceedings of the National Academy of Sciences of the United States of America, 102(14), 5108–5113. https://doi.org/10.1073/pnas.0408725102 Dunbar, B. S., & Schwoebel, E. D. (1990). Preparation of Polyclonal Antibodies. Methods in Enzymology, 182(C), 663–670. https://doi.org/10.1016/0076-6879(90)82051-3 Egan, J., Hoffman, S., Haynes, J., Sadoff, J., Schneider, I., Grau, G., … Gordon, D. (1993). Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. American Journal of Tropical Medicine and Hygiene, 49(2), 166–173. https://doi.org/10.4269/ajtmh.1993.49.166 El-Manzalawy, Y., Dobbs, D., & Honavar, V. (2008). Predicting linear B-cell epitopes using string kernels. J. Mol. Recognit, 21, 243–255. https://doi.org/10.1002/jmr.893 Ellis, R., Martin, L. B., Shaffer, D., Long, C., Miura, K., Fay, M., … Durbin, A. (2010). Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1 42-C1/alhydrogel with and without CPG 7909 in malaria naïve adults. PLoS ONE, 5(1), 1–9. https://doi.org/10.1371/journal.pone.0008787 Esen, M., Kremsner, P., Schleucher, R., Gässler, M., Imoukhuede, E., Imbault, N., … Mordmüller, B. (2009). Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate. Vaccine, 27(49), 6862–6868. https://doi.org/10.1016/j.vaccine.2009.09.011 Espejo, F., Bermúdez, A., Vanegas, M., Rivera, Z., Torres, E., Salazar, L. M., & Patarroyo, M. E. (2005). Elongating modified conserved peptides eliminates their immunogenicity and protective efficacy against P. falciparum malaria. Journal of Structural Biology, 150(3), 245–258. https://doi.org/10.1016/j.jsb.2005.03.007 Espejo, F., Cubillos, M., Mary Salazar, L., Guzmán, F., Urquiza, M., Ocampo, M., … Patarroyo, M E. (2001). Structure, Immunogenicity, and Protectivity Relationship for the 1585 Malarial Peptide and Its Substitution Analogues (Vol. 113). |
| dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| dc.rights.license.spa.fl_str_mv |
Atribución-NoComercial-CompartirIgual 4.0 Internacional |
| dc.rights.uri.spa.fl_str_mv |
http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
Atribución-NoComercial-CompartirIgual 4.0 Internacional http://creativecommons.org/licenses/by-nc-sa/4.0/ http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.extent.spa.fl_str_mv |
[100] páginas |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.coverage.country.spa.fl_str_mv |
Colombia |
| dc.publisher.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.publisher.program.spa.fl_str_mv |
Bogotá - Ciencias - Maestría en Ciencias - Farmacología |
| 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 |
| bitstream.url.fl_str_mv |
https://repositorio.unal.edu.co/bitstream/unal/85352/1/license.txt https://repositorio.unal.edu.co/bitstream/unal/85352/2/Tesis%20de%20Maestr%c3%ada%20en%20Ciencias%20-%20Farmacolog%c3%ada.pdf https://repositorio.unal.edu.co/bitstream/unal/85352/3/Tesis%20de%20Maestr%c3%ada%20en%20Ciencias%20-%20Farmacolog%c3%ada.pdf.jpg |
| bitstream.checksum.fl_str_mv |
eb34b1cf90b7e1103fc9dfd26be24b4a 75d1b7ef81a6fcef6f586cc1c7c720ca dea2b02aba27c8cd178c3c53d2c062c3 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| repository.mail.fl_str_mv |
repositorio_nal@unal.edu.co |
| _version_ |
1814090256978280448 |
| spelling |
Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Lozano Moreno, José Manueldcbd854266c63b771557dc4006002e04Melo Velanida, Fredy Leonardob9a4c2115b5236b8721459d206edcfb5Mimetismo Molecular de Los Agentes Infecciosos2024-01-17T18:32:49Z2024-01-17T18:32:49Z2023-11-07https://repositorio.unal.edu.co/handle/unal/85352Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones a color, diagramas, fotografíasEstudios realizados en el marco de investigación del grupo de mimetismo molecular de los agentes infecciosos, evaluaron la reactividad de sueros de áreas endémicas de Colombia (san juan de nepomuceno - bolívar, tierralta - córdoba, nuquí - chocó y tumaco - nariño) (SIVIGILA, instituto nacional de salud, 2018), frente a lisados de dos cepas de referencia, 3D7 y FCB2 de Plasmodium falciparum, donde se identificaron bandas de reconocimiento de la proteína MSP1 con movilidades relativas de 195, 83, 42 y 38 kDa, que permitieron identificar la reactividad de sueros frente a la proteína precursora MSP1 y sus fragmentos de procesamiento, lo que valida la importancia de este antígeno de superficie respecto a su papel inmunológico, perfilándola como una proteína blanco en la implementación de modificaciones tipo amida reducida, que promuevan y evidencien una protección efectiva de individuos expuestos a la infección natural. (Texto tomado de la fuente)Studies carried out within the research framework of the molecular mimicry of infectious agents group, evaluated the reactivity of sera from endemic areas of Colombia (San Juan de Nepomuceno - Bolívar, Tierralta - Córdoba, Nuquí - Chocó and Tumaco - Nariño) (SIVIGILA, national institute of health, 2018), compared to lysates of two reference strains, 3D7 and FCB2 of Plasmodium falciparum, where recognition bands of the MSP1 protein were identified with relative mobilities of 195, 83, 42 and 38 kDa, which allowed the identification the reactivity of sera against the MSP1 precursor protein and its processing fragments, which validates the importance of this surface antigen with respect to its immunological role, profiling it as a target protein in the implementation of reduced amide type modifications, which promote and demonstrate effective protection of individuals exposed to natural infection.La Convocatoria para el Apoyo a Proyectos de Investigación y Creación Artística de la Sede Bogotá de la Universidad Nacional de Colombia - 2019, tiene como objetivo fortalecer el desarrollo de la investigación y la creación artística, contribuir a la formación en procesos de investigación y extensión de estudiantes de pregrado y posgrado, y generar impacto mediante el reconocimiento y visibilidad de la Universidad Nacional de Colombia de la sede Bogotá, a través de la producción académica asociada al desarrollo de proyectos de investigación.MaestríaMagister en Ciencias - FarmacologíaCiencias Médicas y de la Salud - Biotecnología en Salud[100] páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - FarmacologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéutica610 - Medicina y salud::616 - EnfermedadesSimulación del acoplamiento molecularPlasmodium falciparumPlasmodium bergheiAntígenos de protozoosPlasmodium yoeliiMalaria-Tratamiento farmacológicoTécnicas InmunológicasMolecular docking simulationAntigens, protozoanImmunologic techniquesProteína MSP1Plasmodium falciparum 3D7Plasmodium berghei ANKAPlasmodium yoelii 17XLMalariaModificación amida reducidaAcoplamiento molecularMSP1 proteinReduced amide modificationMolecular dockingExploración de modificaciones estructurales de un antígeno de la proteína MSP1 de Plasmodium spp y su influencia en su propiedad de reconocimiento molecular por sueros murinos y humanos, de personas de áreas postconflicto en ColombiaExploration of structural modifications of an MSP1 protein antigen from Plasmodium spp and their influence on its molecular recognition property by murine and human sera from people from post-conflict areas in ColombiaTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMColombiaAbbas, A. K., Lichtman, A. H., & Pillai, S. (2015). Student Consult (8°; Elsevier, ed.). https://doi.org/10.1016/j.genhosppsych.2013.05.007Acosta, C., Galindo, C., Schellenberg, D., Aponte, J., Kahigwa, E., Urassa, H., … Alonso, P. (1999). Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. Tropical Medicine and International Health, 4(5), 368–376. https://doi.org/10.1046/j.1365-3156.1999.00406.Aikawa M, Miller LH, Johnson J, Rabbege J (1978) Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. J. Cell Biol. 77: 72–82.Akter, J., Khoury, D. S., Aogo, R., Lansink, L. I., SheelaNair, A., Thomas, B. S., … Haque, A. (2019). Plasmodium-specific antibodies block in vivo parasite growth without clearing infected red blood cells. PLoS Pathogens, 15(2), 1–24. https://doi.org/10.1371/journal.ppat.1007599Al-Yaman, F., Genton, B., Anders, R., Falk, M., Triglia, T., Lewis, D., … Alpers, M. (1994). Relationship between humoral response to Plasmodium falciparum merozoite surface antigen- 2 and malaria morbidity in a highly endemic area of Papua New Guinea. American Journal of Tropical Medicine and Hygiene, 51, 593–602. https://doi.org/10.4269/ajtmh.1994.51.593Angulo, I., & Fresno, M. (2002, November). Cytokines in the pathogenesis of and protection against malaria. Clinical and Diagnostic Laboratory Immunology, Vol. 9, pp. 1145–1152. https://doi.org/10.1128/CDLI.9.6.1145-1152.2002Arias-Murillo, Y., Osorio-Arango, K., Bayona, B., Ercilla, Guadalupe., Beltrán-Durán, Mauricio. (2017). Determinación del polimorfismo de HLA-A, -B y -DRB1 en donantes de órganos con muerte encefálica representativos de la población general colombiana, 2007-2014. Biomédica, 37, 184-190. doi: http://dx.doi.org/10.7705/biomedica.v37i2.3263Arlett, H., & Spielmann, T. (2014). Preparation of Parasite Protein Extracts and Western Blot Analysis.In Bio-protocol LLC (Vol. 4).Arnaiz-Villena, A., Muñiz, E., del Palacio-Gruber, J., Campos, C., Alonso-Rubio, J., Gomez-Casado, E., … Silvera, C. (2016). Ancestry of Amerindians and its Impact in Anthropology, Transplantation, HLA Pharmacogenomics and Epidemiology by HLA Study in Wiwa Colombian Population. Open Medicine Journal, 3(1), 269–285. https://doi.org/10.2174/1874220301603010269Arrunategui, A. M., Villegas, A., Ocampo, L. Á., Rodríguez, L. M., & Badih, A. (2013). Frecuencias alélicas, genotípicas y haplotípicas del sistema HLA clase I y II en donantes de una población del suroccidente colombiano. Acta Medica Colombiana, 38(1), 16–21.Aurrecoechea, C., Brestelli, J., Brunk, B., Dommer, J., Fischer, S., Gajria, B., … Wang, H. (2009). PlasmoDB: A functional genomic database for malaria parasites. Nucleic Acids Research, 37(SUPPL. 1), D539. https://doi.org/10.1093/nar/gkn814Ávila-Portillo, L. M., Carmona, A., Franco, L., Briceño, I., Casas, M. C., & Gómez, A. (2010). Bajo polimorfismo en el sistema de antígenos de leucocitos humanos en población mestiza colombiana. Universitas Médica, 51(4), 359–370. https://doi.org/10.11144/javeriana.umed51- 4.bpsaBahl, A., Brunk, B., Crabtree, J., Fraunholz, M., Gajria, B., Grant, G., … Whetzel, P. (2003). PlasmoDB: The Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Research, 31(1), 212–215. https://doi.org/10.1093/nar/gkg081Baird, J. (1998). Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum. Annals of Tropical Medicine and Parasitology, 92(4), 367–390. https://doi.org/10.1080/00034989859366Bannister, L., Hopkins, J., Fowler, R., Krishna, S., & Mitchell, G. (2000). A Brief Illustrated Guide to the Ultrastructure of Plasmodium falciparum Asexual Blood Stages. Parásitology Today, 16(10), 427–433. https://doi.org/10.1016/S0169-4758(00)01755-5Bastian, M., Lozano, J. M., Patarroyo, M. E., Pluschke, G., & Daubenberger, C. A. (2004). Characterization of a reduced peptide bond analogue of a promiscuous CD4 T cell epitope derived from the Plasmodium falciparum malaria vaccine candidate merozoite surface protein 1. Molecular Immunology, 41, 775–784. https://doi.org/10.1016/j.molimm.2004.04.019Batista-Duharte, A., Lastre, M., & Pérez, O. (2014). Adyuvantes inmunológicos. Determinantes en el balance eficacia-toxicidad de las vacunas contemporáneas. Enfermedades Infecciosas y Microbiologia Clinica, 32(2), 106–114. https://doi.org/10.1016/j.eimc.2012.11.012Battle, K., Karhunen, M., Bhatt, S., Gething, P., Howes, R., Golding, N., … Hay, S. (2014). Geographical variation in Plasmodium vivax relapse. Malaria Journal, 13(1), 1–16. https://doi.org/10.1186/1475-2875-13-144Beeson, J., Drew, D., Boyle, M., Feng, G., Fowkes, F., & Richards, J. (2016). Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria. FEMS Microbiology Reviews, 40(3), 343–372. https://doi.org/10.1093/femsre/fuw001Bergmann-Leitner, E., Duncan, E., & Angov, E. (2012). Malaria Vaccine. In O. Okwa (Ed.), The Impact of Immune Responses on the Asexual Erythrocytic Stages of Plasmodium and the Implication for Vaccine Development. https://doi.org/10.5772/33130Bermeo, S., Guerra, M. T., & Ostos Alfonso, H. (2010). Vista de Frecuencias de HLA-A, B y DRB1 en una población de Huila-Colombia. Revista Facultad de Salud, 2(1), 9–19.Bernal, J., & Briceño, I. (2013). Estudios de HLA en Colombia. Acta Medica Colombiana, Vol. 38, pp.5–6.Vol. 38, pp.5–6. P. (1986). Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion. Proceedings of the National Academy of Sciences of the United States of America, 83(4), 1065– 1069. https://doi.org/10.1073/pnas.83.4.1065 Birkett, A. (2016). Status of vaccine research and development of vaccines for malaria. Vaccine, 34, 2915–2920. https://doi.org/10.1016/j.vaccine.2016.02.074Black, C. G., Wang, L., Wu, T., & Coppel, R. L. (2003). Apical location of a novel EGF-like domain- containing protein of Plasmodium falciparum. Molecular and Biochemical Parasitology, 127(1),59–68. https://doi.org/10.1016/S0166-6851(02)00308-0Black, C. G., Wu, T., Wang, L., Hibbs, A. R., & Coppel, R. L. (2001). Merozoite surface protein 8 of Plasmodium falciparum contains two epidermal growth factor-like domains. Molecular and Biochemical Parasitology, 114(2), 217–226. https://doi.org/10.1016/S0166-6851(01)00265-1Blackman, M. J., Heidrich, H. G., Donachie, S., McBride, J. S., & Holder, A. (1990). A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. Journal of Experimental Medicine, 172, 379–382. https://doi.org/10.1084/jem.172.1.379Blackman, M. J., Whittle, H., & Holder, A. (1991). Processing of the Plasmodium falciparum major merozoite surface protein-1: identification of a 33-kilodalton secondary processing product which is shed prior to erythrocyte invasion. Molecular and Biochemical Parasitology, 49, 35–44. https://doi.org/10.1016/0166-6851(91)90128-SBlasco, B., Leroy, Di., & Fidock, D. A. (2017). Antimalarial drug resistance: Linking Plasmodium falciparum parasite biology to the clinic. Nature Medicine, 23(8), 917–928. https://doi.org/10.1038/nm.4381Bohley, P., & Seglen, P. (1992). Proteases and proteolysis in the lysosome. Experientia, 48(2), 151– 157. https://doi.org/10.1007/BF01923508Bonanni, P. (1999). Demographic impact of vaccination: A review. Vaccine, 17(SUPPL. 3), 120–125. https://doi.org/10.1016/S0264-410X(99)00306-0Boyle, M. J., Langer, C., Chan, J. A., Hodder, A., Coppel, R. L., Anders, R., & Beeson, J. (2014). Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum. Infection and Immunity, 82(3), 924–936. https://doi.org/10.1128/IAI.00866-13Cai, Q., Peng, G., Bu, L., Lin, Y., Zhang, L., Lustigmen, S., & Wang, H. (2007). Immunogenicity and in vitro protective efficacy of a polyepitope Plasmodium falciparum candidate vaccine constructed by epitope shuffling. Vaccine, 25(28), 5155–5165. https://doi.org/10.1016/j.vaccine.2007.04.085Camus, D., & Hadley, T. J. (1985). A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science, 230(4725), 553–556. https://doi.org/10.1126/science.3901257Cavanagh, D. R., & McBride, J. S. (1997). Antigenicity of recombinant proteins derived from Plasmodium falciparum merozoite surface protein 1. Molecular and Biochemical Parasitology, 85(2), 197–211. https://doi.org/10.1016/S0166-6851(96)02826-5Céspedes, N., Arévalo-Herrera, M., Felger, I., Reed, S., Kajava, A. V, Corradin, G., & Herrera, S. (2013). Antigenicity and immunogenicity of a novel chimeric peptide antigen based on the P. vivax circumsporozoite protein. Vaccine, 31, 4923–4930. https://doi.org/10.1016/j.vaccine.2013.05.082Chaves, F., Calvo, J., Carvajal, C., Rivera, Z., Ramírez, L., Pinto, M., … Patarroyo, M. E. (2001). Synthesis, isolation and characterization of Plasmodium falciparum antigenic tetrabranched peptide dendrimers obtained by thiazolidine linkages. Journal of Peptide Research, 58(4), 307– 316. https://doi.org/10.1034/j.1399-3011.2001.00921.Chen, J. S., Liu, H., Yang, J., & Chou, K. (2007). Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids, 33, 423–428. https://doi.org/10.1007/s00726-006-0485-9Christopher, A., MacRaild, C. A., Reiling, L., Wycherley, K., Boyle, M. J., Kienzle, V., … Anders, R. (2012). Antigenic characterization of an intrinsically unstructured protein, Plasmodium falciparum merozoite surface protein 2. Infection and Immunity, 80(12), 4177–4185. https://doi.org/10.1128/IAI.00665-12Coffman, R. L., Sher, A., & Seder, R. A. (2010). Vaccine adjuvants: Putting innate immunity to work.Immunity, 33, 492–503. https://doi.org/10.1016/j.immuni.2010.10.002Cohen, S. (1961). Gamma-Globulin and acquired immunity to human malaria. Nature, 192.Coligan, J. E., Bierer, B. E., David, M., Shevach, E., & Strober, W. (2007). Current Protocols in Immunology (Richard Coico, Ed.). https://doi.org/10.1002/0471142735Collins, C. R., & Blackman, M. J. (2011). Apicomplexan AMA1 in Host Cell Invasion: A Model at the Junction? Cell Host & Microbe, 10(6), 531–533. https://doi.org/10.1016/J.CHOM.2011.11.006Coppi, A., Natarajan, R., Pradel, G., Bennett, B. L., James, E. R., Roggero, M. A., … Sinnis, P. (2011). The malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host. Journal of Experimental Medicine, 208(2), 341–356. https://doi.org/10.1084/jem.20101488Coppi, A., Pinzon-Ortiz, C., Hutter, C., & Sinnis, P. (2005). The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion. Journal of Experimental Medicine, 201(1), 27– 33. https://doi.org/10.1084/jem.20040989Corman, V., Müller, M., Costabel, U., Timm, J., Binger, T., Meyer, B., … Drosten, C. (2012). Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillance, 17(49), 20334. https://doi.org/10.2807/ese.17.49.20334Correa, P., Whitworth, W., Kuffner, T., McNicholl, J., & Anaya, J. (2002). HLA-DR and DQB1 gene polymorphism in the North-western Colombian population. Tissue Antigens, 59(5), 436–439. https://doi.org/10.1034/j.1399-0039.2002.590515Cowman, A., Healer, J., Marapana, D., & Marsh, K. (2016, October 20). Malaria: Biology and Disease.Cell, Vol. 167, pp. 610–624. https://doi.org/10.1016/j.cell.2016.07.055Cox, F. (2002, October). History of human parasitology. Clinical Microbiology Reviews, Vol. 15, pp.595–612. https://doi.org/10.1128/CMR.15.4.595-612.2002Crewther, PE., Culvenor, J., Silva, A., Cooper, JA., Anders. RF. (1990). Plasmodium falciparum: two antigens of similar size are located in different compartments of the rhoptry. Exp. Parasitol. 70:193–206Croft, N. P., & Purcell, A. W. (2011). Peptidomimetics: Modifying peptides in the pursuit of better vaccines. Expert Review of Vaccines, 10(2), 211–226. https://doi.org/10.1586/erv.10.161Crompton, P. D., Kayala, M. A., Traore, B., Kayentao, K., Ongoiba, A., Weiss, G. E., … Pierce, S. K. (2010). A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proceedings of the National Academy of Sciences of the United States of America, 107(15), 6958–6963. https://doi.org/10.1073/pnas.1001323107Cubillos, M., Espejo, F., Purmova, J., Martinez, J. C., & Patarroyo, M. E. (2003). Alpha helix shortening in 1522 MSP-1 conserved peptide analogs is associated with immunogenicity and protection against P. falciparum malaria. Proteins: Structure, Function and Genetics, 50(3), 400–409. https://doi.org/10.1002/prot.10314Cuesta Astroz, Yesid, & Segura Latorre, Cesar. (2012). Métodos proteómicos aplicados al estudio de la malaria: Plasmodium falciparum. Acta Biológica Colombiana, 17(3), 463-484. Retrieved January 18, 2022, from http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120- 548X2012000300002&lng=en&tlng=esCulvenor, J., Day, K., & Anders, R. (1991). Plasmodium falciparum ring-infected erythrocyte surface antigen is released from merozoite dense granules after erythrocyte invasion. Infection and Immunity, 59(3), 1183–1187. https://doi.org/10.1128/iai.59.3.1183-1187.1991D’Alessandro, U., Leach, A., Drakeley, C., Bennett, S., Olaleye, B., Fegan, G., … Targett, G. (1995). Efficacy trial of malaria vaccine SPf66 in Gambian infants. Lancet, 346(8973), 462–467. https://doi.org/10.1016/s0140-6736(95)91321-1D’Amelio, E., Salemi, S., & D’Amelio, R. (2015, May 3). Anti-Infectious Human Vaccination in Historical Perspective. International Reviews of Immunology, Vol. 35, pp. 260–290. https://doi.org/10.3109/08830185.2015.1082177Daubenberger, C. A., Nickel, B., Ciatto, C., Grütter, M. G., Pöltl‐Frank, F., Rossi, L., … Pluschke, G. (2002). Amino acid dimorphism and parasite immune evasion: cellular immune responses to a promiscuous epitope of Plasmodium falciparum merozoite surface protein 1 displaying dimorphic amino acid polymorphism are highly constrained. European Journal of Immunology, 32(12), 3667–3677. https://doi.org/10.1002/1521-4141(200212)32:12<3667::AID- IMMU3667>3.0.CO;2-CDavies, E. E. (1974). Ultrastructural studies on the early ookinete stage of Plasmodium berghei nigeriensis and its transformation into an oocyst. Annals of Tropical Medicine and Parasitology, 68(3), 283–290. https://doi.org/10.1080/00034983.1974.11686950De Groot, A. S. (2006, March). Immunomics: Discovering new targets for vaccines and therapeutics.Drug Discovery Today, Vol. 11, pp. 203–209. https://doi.org/10.1016/S1359-6446(05)03720-7De Sousa, K., & Doolan, D. (2016). Immunomics: a 21st century approach to vaccine development for complex pathogens. Parasitology, 143(Special issue), 236–244. https://doi.org/10.1017/S0031182015001079Deans, J., Knight, A., Jean, W., Waters, A., Cohen, S., & Mitchell, G. (1988). Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen. Parasite Immunology, 10(5), 535–552. https://doi.org/10.1111/j.1365-3024.1988.tb00241Dearsly, A., Sinden, R., & Self, I. (1990). Sexual development in malarial parasites: Gametocyte production, fertility and infectivity to the mosquito vector. Parasitology, 100(3), 359–368. https://doi.org/10.1017/S0031182000078628Del Río-Ospina, L., Camargo, M., Soto-De León, S.C., Robayo-Calderón, K.L., Garzón-Ospina, D… (2019). Using next-generation sequencing for characterising HLA-DRB1 and DQB1 loci in a cohort of Colombian women. HLA Immnune Response Genetics, (94)5, 425-434. https://doi.org/10.1111/tan.13672Dhanda, S. K., Gupta, S., Vir, P., & Raghava, G. (2013). Prediction of IL4 Inducing Peptides. Clinical and Developmental Immunology, 2013, 1–9. https://doi.org/10.1155/2013/263952Dhanda, S. K., Vir, P., & Raghava, G. (2013). Designing of interferon-gamma inducing MHC class-II binders. Biology Direct, 8(1), 1–15. https://doi.org/10.1186/1745-6150-8-30Dieng, M. M., Diawara, A., Manikandan, V., Tamim El Jarkass, H., Sermé, S. S., Sombié, S., Idaghdour, Y. (2020). Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria. Nature Communications, 11(1), 1–11. https://doi.org/10.1038/s41467- 020-18915-6Dinko, B., & Pradel, G. (2016). Immune Evasion by Plasmodium falciparum Parasites: Converting a Host Protection Mechanism for the Parasite’s Benefit. Advances in Infectious Diseases, 06, 82– 95. https://doi.org/10.4236/aid.2016.62011Dobaño, C., Sanz, H., Sorgho, H., Dosoo, D., Mpina, M., Ubillos, I., … Gyan, B. (2019). Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/ AS01E malaria vaccine efficacy. Nature Communications, 10(2174), 1–13. https://doi.org/10.1038/s41467-019-10195-zDonahue, CG., Carruthers, v., Gilk, sd., Ward, GE. (2000). The Toxoplasma homolog of Plasmodium apical membrane antigen-1 (AMA-1) is a microneme protein secreted in response to elevated intracellular calcium levels. Mol. Biochem. Parasitol. 111:15–30Doolan, D. (Ed.). (2002). Malaria Methods and Protocols. New Jersey: Humana Press.Doolan, D., Dobaño, C., & Baird, J. (2009). Acquired immunity to Malaria. Clinical Microbiology Reviews, 22(1), 13–36. https://doi.org/10.1128/CMR.00025-08Drakeley, C., Corran, P., Coleman, P., Tongren, J., McDonald, S. L., Carneiro, I., … Riley, E. (2005). Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure. Proceedings of the National Academy of Sciences of the United States of America, 102(14), 5108–5113. https://doi.org/10.1073/pnas.0408725102Dunbar, B. S., & Schwoebel, E. D. (1990). Preparation of Polyclonal Antibodies. Methods in Enzymology, 182(C), 663–670. https://doi.org/10.1016/0076-6879(90)82051-3Egan, J., Hoffman, S., Haynes, J., Sadoff, J., Schneider, I., Grau, G., … Gordon, D. (1993). Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. American Journal of Tropical Medicine and Hygiene, 49(2), 166–173. https://doi.org/10.4269/ajtmh.1993.49.166El-Manzalawy, Y., Dobbs, D., & Honavar, V. (2008). Predicting linear B-cell epitopes using string kernels. J. Mol. Recognit, 21, 243–255. https://doi.org/10.1002/jmr.893Ellis, R., Martin, L. B., Shaffer, D., Long, C., Miura, K., Fay, M., … Durbin, A. (2010). Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1 42-C1/alhydrogel with and without CPG 7909 in malaria naïve adults. PLoS ONE, 5(1), 1–9. https://doi.org/10.1371/journal.pone.0008787Esen, M., Kremsner, P., Schleucher, R., Gässler, M., Imoukhuede, E., Imbault, N., … Mordmüller, B. (2009). Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate. Vaccine, 27(49), 6862–6868. https://doi.org/10.1016/j.vaccine.2009.09.011Espejo, F., Bermúdez, A., Vanegas, M., Rivera, Z., Torres, E., Salazar, L. M., & Patarroyo, M. E. (2005). Elongating modified conserved peptides eliminates their immunogenicity and protective efficacy against P. falciparum malaria. Journal of Structural Biology, 150(3), 245–258. https://doi.org/10.1016/j.jsb.2005.03.007Espejo, F., Cubillos, M., Mary Salazar, L., Guzmán, F., Urquiza, M., Ocampo, M., … Patarroyo, ME. (2001). Structure, Immunogenicity, and Protectivity Relationship for the 1585 Malarial Peptide and Its Substitution Analogues (Vol. 113).Convocatoria para el apoyo a proyectos de investigación y creación artística de la sede Bogotá de la Universidad Nacional de Colombia - 2019Universidad Nacional de ColombiaAdministradoresBibliotecariosConsejerosEstudiantesGrupos comunitariosInvestigadoresMaestrosMedios de comunicaciónPadres y familiasPersonal de apoyo escolarProveedores de ayuda financiera para estudiantesPúblico generalReceptores de fondos federales y solicitantesResponsables políticosLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85352/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINALTesis de Maestría en Ciencias - Farmacología.pdfTesis de Maestría en Ciencias - Farmacología.pdfTesis de Maestría en Ciencias - Farmacologíaapplication/pdf3961254https://repositorio.unal.edu.co/bitstream/unal/85352/2/Tesis%20de%20Maestr%c3%ada%20en%20Ciencias%20-%20Farmacolog%c3%ada.pdf75d1b7ef81a6fcef6f586cc1c7c720caMD52THUMBNAILTesis de Maestría en Ciencias - Farmacología.pdf.jpgTesis de Maestría en Ciencias - Farmacología.pdf.jpgGenerated Thumbnailimage/jpeg4738https://repositorio.unal.edu.co/bitstream/unal/85352/3/Tesis%20de%20Maestr%c3%ada%20en%20Ciencias%20-%20Farmacolog%c3%ada.pdf.jpgdea2b02aba27c8cd178c3c53d2c062c3MD53unal/85352oai:repositorio.unal.edu.co:unal/853522024-01-17 23:03:43.115Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.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 |