Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos

56 páginas : gráficas, ilustraciones

Autores:
Camargo Castañeda, Andrea
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2019
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
Repositorio:
Repositorio Institucional UDCA
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spa
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Acceso en línea:
https://repository.udca.edu.co/handle/11158/2759
Palabra clave:
Fiebre Aftosa
Anticuerpos
Aphthovirus
Virosis
Péptidos
Rights
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License
Derechos Reservados - Universidad de Ciencias Aplicadas y Ambientales
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dc.title.spa.fl_str_mv Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
title Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
spellingShingle Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
Fiebre Aftosa
Anticuerpos
Aphthovirus
Virosis
Péptidos
title_short Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
title_full Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
title_fullStr Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
title_full_unstemmed Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
title_sort Título de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinos
dc.creator.fl_str_mv Camargo Castañeda, Andrea
dc.contributor.advisor.spa.fl_str_mv Avendaño Valenzuela, Catalina Esther, dir.
dc.contributor.author.spa.fl_str_mv Camargo Castañeda, Andrea
dc.subject.mesh.spa.fl_str_mv Fiebre Aftosa
Anticuerpos
Aphthovirus
topic Fiebre Aftosa
Anticuerpos
Aphthovirus
Virosis
Péptidos
dc.subject.agrovoc.spa.fl_str_mv Virosis
Péptidos
description 56 páginas : gráficas, ilustraciones
publishDate 2019
dc.date.issued.spa.fl_str_mv 2019
dc.date.accessioned.spa.fl_str_mv 2020-02-13T13:57:42Z
dc.date.available.spa.fl_str_mv 2020-02-13T13:57:42Z
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dc.relation.references.spa.fl_str_mv Arzt, J., Juleff, N., Zhang, Z., & Rodriguez, L. L. (2011). The Pathogenesis of Footand-Mouth Disease I: Viral Pathways in Cattle. Transboundary and Emerging Diseases, 58(4), 291–304. https://doi.org/10.1111/j.1865-1682.2011.01204.x
Baxter, R., Craigmile, S. C., Haley, C., Douglas, A. J., Williams, J. L., & Glass, E. J. (2009). BoLA-DR peptide binding pockets are fundamental for foot-and-mouth disease virus vaccine design in cattle. Vaccine, 28(1), 28–37. https://doi.org/10.1016/j.vaccine.2009.09.131
Behl, J. D., Verma, N. K., Tyagi, N., Mishra, P., Behl, R., & Joshi, B. K. (2012). The Major Histocompatibility Complex in Bovines: A Review. ISRN Veterinary Science, 2012, 1–12. https://doi.org/10.5402/2012/872710
Brown, C. C., Meyer, R. F., Olander, H. J., House, C., & Mebus, C. A. (1992). A pathogenesis study of foot-and-mouth disease in cattle, using in situ hybridization. Canadian Journal of Veterinary Research = Revue Canadienne de Recherche Vétérinaire, 56(3), 189–193.
Cao, Y., Lu, Z., & Liu, Z. (2016). Foot-and-mouth disease vaccines: progress and problems. Expert Review of Vaccines, 15(6), 783–789. https://doi.org/10.1586/14760584.2016.1140042
Clem, A. S. (2011). Fundamentals of vaccine immunology. Journal of Global Infectious Diseases, 3(1), 73–78. https://doi.org/10.4103/0974-777X.77299
FAO. (2018). Foot-and-Mouth Disease Situation November 2018. Retrieved from http://www.fao.org/fileadmin/user_upload/eufmd/FMD_reports_GMR/Novembe r_GMR_2018.pdf
Gao, Y., Sun, S. Q., & Guo, H. C. (2016). Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements. Virology Journal, 13(1), 1–17. https://doi.org/10.1186/s12985-016-0561-z
Grubman, M. J. (2006). New approaches to control foot-and-mouth disease: antivirals and novel vaccines. Rev Col Cienc Pec, 19(3), 341.
Grubman, M. J., & Baxt, B. (2004). Foot-and-mouth disease. Clinical Microbiology Reviews, 17(2), 465–493. https://doi.org/10.1128/CMR.17.2.465
ICA. (2013). Colombia, Sanidad Animal 2013. Igarss 2014, (1), 1–5. https://doi.org/10.1007/s13398-014-0173-7.2
ICA. (2017a). Al culminar el sacrificio y enterramiento sanitario de más de 3.300 animales, ICA confirma que se concluyeron los casos activos de aftosa en el país. Bogota, Colombia. Retrieved from http://www.ica.gov.co/Noticias/Pecuaria/Al-culminar-el-sacrificio-yenterramiento-sanitari.aspx
ICA. (2017b). Colombia notifica ante la Organización Mundial de Sanidad Animal, un foco de fiebre aftosa. Bogotá, Colombia. Retrieved from http://www.ica.gov.co/Noticias/Pecuaria/Colombia-notifica-ante-laOrganizacion-Mundial-de.aspx
ICA. (2019). Vacunación Contra La Fiebre Aftosa. Proyectos Estratégicos ICA. Retrieved from https://www.ica.gov.co/getdoc/10c3264c-97db-4cfa-9c0b92d0f2eae8c7/vacunacion.aspx
Jamal, S. M., & Belsham, G. J. (2013). Foot-and-mouth disease: Past, present and future. Veterinary Research, 44(1), 116. https://doi.org/10.1186/1297-9716-44- 116
Kamel, M., El-Sayed, A., & Castañeda Vazquez, H. (2019). Foot-and-mouth disease vaccines: recent updates and future perspectives. Archives of Virology, (0123456789). https://doi.org/10.1007/s00705-019-04216-x
King, D. P., Ludi, A., Wilsden, G., Parida, S., & Paton, D. J. (2015). The use of nonstructural proteins to differentiate between vaccinated and infected animals, 1– 4. Retrieved from http://www.oie.int/fileadmin/Home/eng/Publications_%26_Documentation/docs /pdf/TT/2015_MO2_King.pdf
Knowles, N. J., & Samuel, A. R. (2015). Foot-and-mouth disease type O viruses exhibit genetically and geographically distinct evolutionary lineages (topotypes). Journal of General Virology, 82(3), 609–621. https://doi.org/10.1099/0022- 1317-82-3-609
Lozano, J. M., Lesmes, L. P., Carreno, L. F., Gallego, G. M., & Patarroyo, M. E. (2010). Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria. Molecules, 15(12), 8856–8889. https://doi.org/10.3390/molecules15128856
Manzoor, S., Ahmed, A., & Abubakar, M. (2015). Comparison of ELISA and Serum Neutralization Test for Detection of Age-Specific Foot and Mouth Disease Virus Antibodies. Veterinary Sciences: Research and Reviews, 2–6.
Medina, G. N., Segundo, F. D.-S., Stenfeldt, C., Arzt, J., & de los Santos, T. (2018). The Different Tactics of Foot-and-Mouth Disease Virus to Evade Innate Immunity. Frontiers in Microbiology, 9(November), 1–22. https://doi.org/10.3389/fmicb.2018.02644
Metwally, S., Ferrari, G., Paton, D., Duffy, S., Bartels, C., & Knight-jones, T. (2016). Foot and mouth disease vaccination and post-vaccination monitoring. (S. Metwally & S. Münstermann, Eds.). The Food and Agriculture Organization of the United Nations and the World Organisation for Animal Health.
Mohan, M. S., Gajendragad, M. R., & Kishore, S. (2009). Kinetics of immune response to foot-and-mouth disease virus ( type Asia 1 ) in experimental cattle, 103–109. https://doi.org/10.1007/s11259-008-9076-4
OIE. (2004). Manual de las pruebas de diagnóstico y de las vacunas para los animales terrestres (mamíferos, aves y abejas ) Volumen I.
OIE. (2016). Foot and mouth disease vaccination and post-vaccination monitoring. (S. Metwally & S. Münstermann, Eds.). The Food and Agriculture Organization of the United Nations and the World Organisation for Animal Health.
OIE. (2019). Foot and Mouth Disease Exercise. Retrieved from http://www.oie.int/en/animal-health-in-the-world/official-disease-status/fmd/en-fmd-carte/
Pacheco, J. M., Arzt, J., & Rodriguez, L. L. (2010). Early events in the pathogenesis of foot-and-mouth disease in cattle after controlled aerosol exposure. Veterinary Journal, 183(1), 46–53. https://doi.org/10.1016/j.tvjl.2008.08.023
Patarroyo, M. E., Cifuentes, G., Bermúdez, A., & Patarroyo, M. A. (2008). Strategies for developing multi-epitope, subunit-based, chemically synthesized antimalarial vaccines. Journal of Cellular and Molecular Medicine, 12(5B), 1915– 1935. https://doi.org/10.1111/j.1582-4934.2008.00174.x
Reid, S. M., Ferris, N. P., Brüning, A., Hutchings, G. H., Kowalska, Z., & Åkerblom, L. (2001). Development of a rapid chromatographic strip test for the pen-side detection of foot-and-mouth disease virus antigen. Journal of Virological Methods, 96(2), 189–202. https://doi.org/10.1016/S0166-0934(01)00334-2
Rweyemamu, M., Roeder, P., MacKay, D., Sumption, K., Brownlie, J., Leforban, Y., … Saraiva, V. (2008). Epidemiological patterns of foot-and-mouth disease worldwide. Transboundary and Emerging Diseases, 55(1), 57–72. https://doi.org/10.1111/j.1865-1682.2007.01013.x
Scheiblhofer, S., Laimer, J., Machado, Y., Weiss, R., & Thalhamer, J. (2017). Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert Review of Vaccines, 16(5), 479–489. https://doi.org/10.1080/14760584.2017.1306441
Şevik, M., & Özürk, F. F. (2013). Comparative evaluation of liquid-phase blocking ELISA and solid-phase competition ELISA methods for the detection of antibodies to the structural proteins of foot-and- mouth disease types O and A viruses. Turkish Journal of Veterinary and Animal Sciences, 37(8), 523–528. https://doi.org/10.3906/vet-1303-26
Skwarczynski, M., & Totha, I. (2016). Chemical Science Peptide-based synthetic vaccines. Chemical Science, 7(12), 842–854. https://doi.org/10.1039/C5SC03892H
Sørensen, K. J., Madsen, K. G., Madsen, E. S., Salt, J. S., Nqindi, J., & Mackay, D. K. J. (1998). Differentiation of infection from vaccination in foot-and-mouth disease by the detection of antibodies to the non-structural proteins 3D, 3AB and 3ABC in ELISA using antigens expressed in baculovirus. Archives of Virology, 143(8), 1461–1476. https://doi.org/10.1007/s007050050390
Soria, I., Quattrocchi, V., Langellotti, C., Pérez-Filgueira, M., Pega, J., Gnazzo, V., … Zamorano, P. (2018). Immune response and partial protection against heterologous foot-and-Mouth disease virus induced by dendrimer peptides in cattle. Journal of Immunology Research, 2018(April), 1–12. https://doi.org/10.1155/2018/3497401
Summerfield, A., Guzylack-Piriou, L., Harwood, L., & McCullough, K. C. (2009). Innate immune responses against foot-and-mouth disease virus: Current understanding and future directions. Veterinary Immunology and Immunopathology, 128(1–3), 205–210. https://doi.org/10.1016/j.vetimm.2008.10.296
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Yang, H., & Kim, D. S. (2015). Peptide Immunotherapy in Vaccine Development, 1– 14. https://doi.org/10.1016/bs.apcsb.2015.03.001
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spelling Avendaño Valenzuela, Catalina Esther, dir.Camargo Castañeda, Andrea2020-02-13T13:57:42Z2020-02-13T13:57:42Z2019https://repository.udca.edu.co/handle/11158/2759MV024 C15t 2019 (205842)56 páginas : gráficas, ilustracionesLa Fiebre Aftosa es considerada como una de las enfermedades más importantes de los animales ungulados, es decir, bovinos, porcinos, caprinos, ovinos y bufalinos tanto domésticos como salvajes. Esta enfermedad es causada por un virus perteneciente al género Aphthovirus de la familia Picornaviridae y ha estado presente en prácticamente todo el mundo. Hoy en día, sigue afectando a más de 100 países, causando importantes pérdidas económicas. La vacunación es una de las principales herramientas probadas para manejar y hasta eliminar la enfermedad, el problema es que las vacunas comerciales usan el virus inactivado y esto puede causar respuestas alérgicas. Además, la inactivación de tales vacunas no siempre es perfecta y el patógeno puede volver a su estado virulento. El posible vertimiento del patógeno al medio ambiente, la mala estabilidad y la necesidad de una cadena de frío para conservar la vacuna, son otras desventajas significativas de las vacunas convencionales. La mayor desventaja de las vacunas convencionales es que estas son diseñadas para inmunizar al animal con cepas (serotipo) específicas. Una alternativa novedosa para resolver estos inconvenientes es diseñar una vacuna usando péptidos químicamente modificados. En este trabajo se analizó la capacidad de seroneutralización “in vitro”. de los anticuerpos producidos en animales vacunados con el candidato vacunal al enfrentar anticuerpos del suero contra los serotipos A24 Cruzeiro y O1 Campos del virus vivo. Para identificar y analizar la eficacia de los anticuerpos producidos contra la FA, se realizó la microprueba cuantitativa de neutralización viral sugerida por la OIE. Se trabajó con el suero de 23 bovinos (17 animales inmunizados con la formulación péptido + adyuvante Montanide ISA 70M, 3 animales vacunados con la vacuna convencional, 2 animales control adyuvante y 1 animal centinela). Para verificar que no existieran anticuerpos frente a los péptidos que se querían probar, se usaron los sueros obtenidos en la sangría inicial y posteriormente, se trabajó con los sueros obtenidos el día 43 post primera inmunización. Se observó que hubo una seroneutralización del 79.6% cuando los sueros fueron enfrentados al virus vivo del serotipo A24, mientras que al ser el enfrentamiento con el serotipo O1 hubo una seroneutralización menor (41.2%). Ningún animal centinela o control adyuvante tuvo títulos mayores a 1:45, y la vacuna convencional alcanzó títulos mayores de 1:6000. Estos valores indican que la prueba se realizó en condiciones ideales, que favorecieron resultados válidos. Para ser la primera formulación peptídica, la producción y neutralización de los anticuerpos generados contra el virus fue muy buena en ambos serotipos. Es importante seguir realizando estudios que aporten al conocimiento de las vacunas peptídicas. Esta técnica se usa actualmente para la formulación de la vacuna contra la malaria y en un futuro podría ser la forma más eficiente de fabricar todo tipo de vacunas. En el caso de la fiebre aftosa, es importante realizar pruebas de VNT frente a otros serotipos (C, SAT1, SAT2, SAT3 y Asia 1) para determinar si la vacuna sintética es apta para su distribución mundial.Foot and Mouth Disease is considered one of the most important diseases of ungulates. It can affect, cattle, pigs, goats, sheep and buffaloes both domestic and wild. This disease is caused by a virus belonging to the genus Aphthovirus of the Picornaviridae family and has been present all over the world. Today, it continues to affect more than 100 countries, causing significant economic losses. Vaccination is one of the main tools tested to manage and even eliminate the disease, the problem is that commercial vaccines use the inactivated virus, and this can cause allergic reactions. In addition, the inactivation of such vaccines is not always perfect, and the pathogen can return to its virulent state. The possible liberation of the pathogen into the environment, poor stability and the need for a cold chain to preserve the vaccine are other significant disadvantages of conventional vaccines. The major problem of conventional vaccines is that they are designed to immunize the animal with specific strains (serotypes). A novel alternative to solve these problems is to design a vaccine using chemically modified peptides. In this work we analyzed the ability of "in vitro" seroneutralization. of the antibodies produced in animals vaccinated with the vaccine candidate when facing serum antibodies against serotypes A24 Cruzeiro and O1 Fields of the live virus. In order to identify and analyze the efficacy of the antibodies produced against AF, the quantitative micro neutralization test suggested by the OIE was performed. We worked with the serum of 23 cattle (17 animals immunized with the Montanide ISA 70M peptide + adjuvant formulation, 3 animals vaccinated with the conventional vaccine, 2 adjuvant control animals and 1 sentinel animal). To verify that there were no antibodies against the peptides that were to be tested, the sera obtained in the initial bleeding were used and subsequently, the sera obtained on day 43 post first immunization were worked on. It was observed that there was a 79.6% seroneutralization when the sera were confronted with the live virus of serotype A24, while being the confrontation with serotype O1 there was a minor seroneutralization (41.2%). No sentinel animal or adjuvant control had titers greater than 1:45, and the conventional vaccine reached titers greater than 1: 6000. These values indicate that the test was performed under ideal conditions, which favored valid results. To be the first peptide formulation, the production and neutralization of antibodies generated against the virus was very good in both serotypes. It is important to continue conducting studies that contribute to the knowledge of peptide vaccines. This technique is currently used for the formulation of the malaria vaccine and in the future could be the most efficient way to manufacture all types of vaccines. In the case of foot and mouth disease, it is important to perform VNT tests against other serotypes (C, SAT1, SAT2, SAT3 and Asia 1) to determine if the synthetic vaccine is suitable for worldwide distribution.Incluye bibliografíaPregradoMédico(a) Veterinarioapplication/pdfspaBogotá : Universidad de Ciencias Aplicadas y Ambientales, 2019Facultad de Ciencias AgropecuariasMedicina VeterinariaDerechos Reservados - Universidad de Ciencias Aplicadas y Ambientaleshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2Fiebre AftosaAnticuerposAphthovirusVirosisPéptidosTítulo de la evaluación de la capacidad de seroneutralización "in vitro" de los anticuerpos generados frente a péptidos químicamente sintetizados y modificados para el control de la fiebre aftosa en bovinosTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/redcol/resource_type/TPhttp://purl.org/coar/version/c_970fb48d4fbd8a85Arzt, J., Juleff, N., Zhang, Z., & Rodriguez, L. L. (2011). The Pathogenesis of Footand-Mouth Disease I: Viral Pathways in Cattle. Transboundary and Emerging Diseases, 58(4), 291–304. https://doi.org/10.1111/j.1865-1682.2011.01204.xBaxter, R., Craigmile, S. C., Haley, C., Douglas, A. J., Williams, J. L., & Glass, E. J. (2009). BoLA-DR peptide binding pockets are fundamental for foot-and-mouth disease virus vaccine design in cattle. Vaccine, 28(1), 28–37. https://doi.org/10.1016/j.vaccine.2009.09.131Behl, J. D., Verma, N. K., Tyagi, N., Mishra, P., Behl, R., & Joshi, B. K. (2012). The Major Histocompatibility Complex in Bovines: A Review. ISRN Veterinary Science, 2012, 1–12. https://doi.org/10.5402/2012/872710Brown, C. C., Meyer, R. F., Olander, H. J., House, C., & Mebus, C. A. (1992). A pathogenesis study of foot-and-mouth disease in cattle, using in situ hybridization. Canadian Journal of Veterinary Research = Revue Canadienne de Recherche Vétérinaire, 56(3), 189–193.Cao, Y., Lu, Z., & Liu, Z. (2016). Foot-and-mouth disease vaccines: progress and problems. Expert Review of Vaccines, 15(6), 783–789. https://doi.org/10.1586/14760584.2016.1140042Clem, A. S. (2011). Fundamentals of vaccine immunology. Journal of Global Infectious Diseases, 3(1), 73–78. https://doi.org/10.4103/0974-777X.77299FAO. (2018). Foot-and-Mouth Disease Situation November 2018. Retrieved from http://www.fao.org/fileadmin/user_upload/eufmd/FMD_reports_GMR/Novembe r_GMR_2018.pdfGao, Y., Sun, S. Q., & Guo, H. C. (2016). Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements. Virology Journal, 13(1), 1–17. https://doi.org/10.1186/s12985-016-0561-zGrubman, M. J. (2006). New approaches to control foot-and-mouth disease: antivirals and novel vaccines. Rev Col Cienc Pec, 19(3), 341.Grubman, M. J., & Baxt, B. (2004). Foot-and-mouth disease. Clinical Microbiology Reviews, 17(2), 465–493. https://doi.org/10.1128/CMR.17.2.465ICA. (2013). Colombia, Sanidad Animal 2013. 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en las Obras Colectivas;
b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda;
c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas.Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).
4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:
a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).
b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.
c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.
d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.
ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.
e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, Acinpro), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.
5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
7. Término.
a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.
b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.
8. Varios.
a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.
b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.
c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.
d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.

