Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose

Detalhes bibliográficos
Autor(a) principal: Barros, Heber Leão Silva
Data de Publicação: 2020
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/31282
http://doi.org/10.14393/ufu.te.2020.738
Resumo: Toxoplasmosis, a zoonosis caused by the mandatory intracellular protozoan Toxoplasma gondii, is a disease virtually capable of infecting any homeothermic host, with cases recorded in several species of birds and mammals, including humans. This disease is relevant not only for humans, since infection with this protozoan is associated with substantial financial losses in livestock, especially in sheep and goats. Infected humans can be asymptomatic or have several different symptoms, the most serious of which are usually seen in individuals who belong to the groups at risk for this disease, such as immunocompromised patients or pregnant women whose concepts can be infected. In the hypothesis of vertical transmission from the pregnant woman to the fetus, toxoplasmosis can cause several symptoms, which can be less severe, such as cases of mild chorioretinitis, even the most severe manifestations, characterized by malformations of the central nervous system from fetus and even intrauterine death and abortion. For immunocompromised individuals, toxoplasmosis also constitutes significant risks, since latent parasitic cysts in the central nervous system can reactivate the inflammatory process, causing neurotoxoplasmosis, which can be fatal. Although it is capable of causing great damage to the host, possibly leading to death or causing sequelae that impair the quality of life of the affected person for the rest of his life, this disease continues to be neglected. As a result of the lack of vigilance and awareness about this disease, both by health professionals and the population in general, several outbreaks occur annually in our country and around the world, always being characterized by the delay in reaching the correct diagnosis. In the present work, we studied an alternative that can mitigate the effects of this disease through the principle of immunoprophylaxis. To achieve this goal, three peptides were predicted containing 15 amino acid residues each, using available prediction tools with the potential to act as epitopes for B cells. The regions were analyzed looking for the two most immunodominant sequences of the secreted protein 8 by the Micronema organelle (MIC8) and one of the sequences related to 52A surface antigens (SRS52A). The synthesized peptides were added immunoadjuvant compounds, such as aluminum hydroxide, or lectin derived from Synadenium carinatum (ScLL), or propranolol, which were used to immunize mice. Tests were carried out to quantify the levels of antibodies and cytokines produced, in addition to the parameters of survival and parasitic load after 30 days of infection. It was observed that all animals immunized with peptides produced specific antibodies to the original protein, except for groups immunized with propranolol. Regarding the analysis of produced cytokines, the groups immunized with ScLL had lower concentrations of cytokines than the non-immunized group, however the ratio of cytokines of the Th1 profile to Th2 was higher. In addition, the animals immunized with peptides and ScLL survived longer than those not immunized, although the difference was not statistically significant. Finally, the parasitic load, when the ScLL group was present, was significantly lower, being around 25% of the load observed in the non-immunized animals. In summary, the results obtained demonstrate that the predicted peptides retained their immunodominant characteristics and, together with ScLL, were able to induce a more effective response against infection, particularly in relation to the chronic phase, thus presenting itself as a potential tool in future prevention studies in the epidemiological chain of toxoplasmosis.
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spelling Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmoseEvaluation of epitopes derived from microneme MIC8 and surface antigen SRS52A from Toxoplasma gondii, associated with different adjuvants, as possible vaccine antigens against toxoplasmosisToxoplasma gondiiMicronema MIC8Antígeno SRS52APeptídeos sintéticosNovos adjuvantesProtocolos vacinaisImmunizationPeptidesNovel adjuvantsPlant extractToxoplasmosisCNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIACNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOSToxoplasma gondiiPeptídeosToxoplasmosis, a zoonosis caused by the mandatory intracellular protozoan Toxoplasma gondii, is a disease virtually capable of infecting any homeothermic host, with cases recorded in several species of birds and mammals, including humans. This disease is relevant not only for humans, since infection with this protozoan is associated with substantial financial losses in livestock, especially in sheep and goats. Infected humans can be asymptomatic or have several different symptoms, the most serious of which are usually seen in individuals who belong to the groups at risk for this disease, such as immunocompromised patients or pregnant women whose concepts can be infected. In the hypothesis of vertical transmission from the pregnant woman to the fetus, toxoplasmosis can cause several symptoms, which can be less severe, such as cases of mild chorioretinitis, even the most severe manifestations, characterized by malformations of the central nervous system from fetus and even intrauterine death and abortion. For immunocompromised individuals, toxoplasmosis also constitutes significant risks, since latent parasitic cysts in the central nervous system can reactivate the inflammatory process, causing neurotoxoplasmosis, which can be fatal. Although it is capable of causing great damage to the host, possibly leading to death or causing sequelae that impair the quality of life of the affected person for the rest of his life, this disease continues to be neglected. As a result of the lack of vigilance and awareness about this disease, both by health professionals and the population in general, several outbreaks occur annually in our country and around the world, always being characterized by the delay in reaching the correct diagnosis. In the present work, we studied an alternative that can mitigate the effects of this disease through the principle of immunoprophylaxis. To achieve this goal, three peptides were predicted containing 15 amino acid residues each, using available prediction tools with the potential to act as epitopes for B cells. The regions were analyzed looking for the two most immunodominant sequences of the secreted protein 8 by the Micronema organelle (MIC8) and one of the sequences related to 52A surface antigens (SRS52A). The synthesized peptides were added immunoadjuvant compounds, such as aluminum hydroxide, or lectin derived from Synadenium carinatum (ScLL), or propranolol, which were used to immunize mice. Tests were carried out to quantify the levels of antibodies and cytokines produced, in addition to the parameters of survival and parasitic load after 30 days of infection. It was observed that all animals immunized with peptides produced specific antibodies to the original protein, except for groups immunized with propranolol. Regarding the analysis of produced cytokines, the groups immunized with ScLL had lower concentrations of cytokines than the non-immunized group, however the ratio of cytokines of the Th1 profile to Th2 was higher. In addition, the animals immunized with peptides and ScLL survived longer than those not immunized, although the difference was not statistically significant. Finally, the parasitic load, when the ScLL group was present, was significantly lower, being around 25% of the load observed in the non-immunized animals. In summary, the results obtained demonstrate that the predicted peptides retained their immunodominant characteristics and, together with ScLL, were able to induce a more effective response against infection, particularly in relation to the chronic phase, thus presenting itself as a potential tool in future prevention studies in the epidemiological chain of toxoplasmosis.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorTese (Doutorado)A toxoplasmose, zoonose causada pelo protozoário intracelular obrigatório Toxoplasma gondii, é um parasita virtualmente capaz de infectar qualquer hospedeiro homeotérmico, possuindo casos registrados em diversas espécies de aves e mamíferos, incluindo humanos. Essa doença apresenta relevância não somente para os seres humanos, uma vez que a infecção por este protozoário está associada a perdas financeiras substanciais na pecuária, principalmente na ovina e caprina. Humanos infectados podem ser assintomáticos ou apresentar diversos sintomas diferentes, sendo que os mais graves usualmente são observados em indivíduos que pertencem aos grupos de risco para essa doença, como os pacientes imunocomprometidos ou gestantes cujos conceptos podem ser infectados. Na hipótese da transmissão vertical da gestante para o concepto, a toxoplasmose pode causar diversos sintomas, que podem ser menos graves, como casos de coriorretinite brandas, até as manisfestações mais severas, caracterizados por mal-formações do sistema nervoso central do feto e até mesmo morte intra-uterina e aborto. Para indivíduos imunocomprometidos, a toxoplasmose também representa riscos significativos, uma vez que os cistos parasitários latentes no sistema nervoso central podem reativar o processo inflamatório, causando neurotoxoplasmose, que pode ser fatal. Ainda que seja capaz de causar grande dano ao hospedeiro, possivelmente levando a óbito ou causando sequelas que prejudiquem a qualidade de vida do indivíduo afetado pelo restante de sua vida, essa doença continua a ser negligenciada. Fruto da falta de vigilância e conscientização sobre essa doença, tanto por parte de profissionais da saúde como da população em geral, acontecem anualmente diversos surtos em nosso país e em todo o mundo, sendo sempre caracterizada pela demora em chegar ao diagnóstico correto. No presente trabalho, estudamos uma alternativa que possa amenizar os efeitos dessa doença por meio do princípio da imunoprofilaxia. Para atingir esse objetivo, foi realizada a predição de três peptídeos contendo 15 resíduos de aminoácidos cada, por meio de ferramentas de predição disponíveis com potencial para atuarem como epitopos para células B. Os trechos foram analisados a partir de duas sequências mais imunodominantes da proteína 8 secretada pela organela Micronema (MIC8) e 1 da sequência relacionada a antígenos de superfície 52A (SRS52A). Aos peptídeos sintetizados foram adicionados compostos imunoadjuvantes, como hidróxido de alumínio, ou lectina derivada de Synadenium carinatum (ScLL), ou propranolol, os quais foram utilizados para imunizar camundongos. Foram realizados ensaios para quantificar os níveis de anticorpos e de citocinas produzidos, em adição aos parâmetros de sobrevivência e da carga parasitária após 30 dias de infecção. Observou-se que todos os animais imunizados com peptídeos produziram anticorpos específicos à proteína original, exceto pelos grupos imunizados com propranolol. Em relação à análise de citocinas produzidas, os grupos imunizados com peptídeos + ScLL tiveram menores concentrações de citocinas, comparados ao grupo não imunizado, porém a razão de citocinas do perfil Th1 por Th2 foi mais alta nos grupos em que o ScLL esteve presente como adjuvante. Além disso, os animais imunizados com peptídeos e ScLL sobreviveram um tempo maior do que os não imunizados, ainda que a diferença não tenha sido estatisticamente significativa. Por fim, a carga parasitária, nos grupos de animais imunizados com formulação na qual ScLL esteve presente, foi significativamente menor, ficando em cerca de 25% da carga observada nos animais não imunizados. Em síntese, os resultados obtidos demonstram que os peptídeos preditos conservaram suas características imunodominantes e juntamente com ScLL, foram capazes de induzir uma resposta de maior eficácia contra a infecção, particularmente em relação à fase crônica, apresentando-se, portanto, como uma ferramenta potencial em estudos futuros de prevenção na cadeia epidemiológica da toxoplasmose.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Imunologia e Parasitologia AplicadasMineo, José Robertohttp://lattes.cnpq.br/2006638367304868Santana, Silas Silvahttp://lattes.cnpq.br/2742248161106428Cunha Junior, Jair Pereira dahttp://lattes.cnpq.br/3571099738256685Gomes, Angelica de Oliveirahttp://lattes.cnpq.br/7824516128256935Simamoto, Bruna Barbosa de Sousahttp://lattes.cnpq.br/8964521363538559Barros, Heber Leão Silva2021-02-18T16:54:09Z2021-02-18T16:54:09Z2020-03-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfBARROS, Heber Leão Silva. Avaliação de epítopos derivados de micronema MIC8 e de antígeno de superfície SRS52A de Toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose. 2020. 76 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Uberlândia, Uberlândia, 2020. DOI http://doi.org/10.14393/ufu.te.2020.738.https://repositorio.ufu.br/handle/123456789/31282http://doi.org/10.14393/ufu.te.2020.738porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2021-03-08T13:26:10Zoai:repositorio.ufu.br:123456789/31282Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2021-03-08T13:26:10Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
Evaluation of epitopes derived from microneme MIC8 and surface antigen SRS52A from Toxoplasma gondii, associated with different adjuvants, as possible vaccine antigens against toxoplasmosis
title Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
spellingShingle Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
Barros, Heber Leão Silva
Toxoplasma gondii
Micronema MIC8
Antígeno SRS52A
Peptídeos sintéticos
Novos adjuvantes
Protocolos vacinais
Immunization
Peptides
Novel adjuvants
Plant extract
Toxoplasmosis
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
CNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS
Toxoplasma gondii
Peptídeos
title_short Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
title_full Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
title_fullStr Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
title_full_unstemmed Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
title_sort Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose
author Barros, Heber Leão Silva
author_facet Barros, Heber Leão Silva
author_role author
dc.contributor.none.fl_str_mv Mineo, José Roberto
http://lattes.cnpq.br/2006638367304868
Santana, Silas Silva
http://lattes.cnpq.br/2742248161106428
Cunha Junior, Jair Pereira da
http://lattes.cnpq.br/3571099738256685
Gomes, Angelica de Oliveira
http://lattes.cnpq.br/7824516128256935
Simamoto, Bruna Barbosa de Sousa
http://lattes.cnpq.br/8964521363538559
dc.contributor.author.fl_str_mv Barros, Heber Leão Silva
dc.subject.por.fl_str_mv Toxoplasma gondii
Micronema MIC8
Antígeno SRS52A
Peptídeos sintéticos
Novos adjuvantes
Protocolos vacinais
Immunization
Peptides
Novel adjuvants
Plant extract
Toxoplasmosis
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
CNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS
Toxoplasma gondii
Peptídeos
topic Toxoplasma gondii
Micronema MIC8
Antígeno SRS52A
Peptídeos sintéticos
Novos adjuvantes
Protocolos vacinais
Immunization
Peptides
Novel adjuvants
Plant extract
Toxoplasmosis
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
CNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS
Toxoplasma gondii
Peptídeos
description Toxoplasmosis, a zoonosis caused by the mandatory intracellular protozoan Toxoplasma gondii, is a disease virtually capable of infecting any homeothermic host, with cases recorded in several species of birds and mammals, including humans. This disease is relevant not only for humans, since infection with this protozoan is associated with substantial financial losses in livestock, especially in sheep and goats. Infected humans can be asymptomatic or have several different symptoms, the most serious of which are usually seen in individuals who belong to the groups at risk for this disease, such as immunocompromised patients or pregnant women whose concepts can be infected. In the hypothesis of vertical transmission from the pregnant woman to the fetus, toxoplasmosis can cause several symptoms, which can be less severe, such as cases of mild chorioretinitis, even the most severe manifestations, characterized by malformations of the central nervous system from fetus and even intrauterine death and abortion. For immunocompromised individuals, toxoplasmosis also constitutes significant risks, since latent parasitic cysts in the central nervous system can reactivate the inflammatory process, causing neurotoxoplasmosis, which can be fatal. Although it is capable of causing great damage to the host, possibly leading to death or causing sequelae that impair the quality of life of the affected person for the rest of his life, this disease continues to be neglected. As a result of the lack of vigilance and awareness about this disease, both by health professionals and the population in general, several outbreaks occur annually in our country and around the world, always being characterized by the delay in reaching the correct diagnosis. In the present work, we studied an alternative that can mitigate the effects of this disease through the principle of immunoprophylaxis. To achieve this goal, three peptides were predicted containing 15 amino acid residues each, using available prediction tools with the potential to act as epitopes for B cells. The regions were analyzed looking for the two most immunodominant sequences of the secreted protein 8 by the Micronema organelle (MIC8) and one of the sequences related to 52A surface antigens (SRS52A). The synthesized peptides were added immunoadjuvant compounds, such as aluminum hydroxide, or lectin derived from Synadenium carinatum (ScLL), or propranolol, which were used to immunize mice. Tests were carried out to quantify the levels of antibodies and cytokines produced, in addition to the parameters of survival and parasitic load after 30 days of infection. It was observed that all animals immunized with peptides produced specific antibodies to the original protein, except for groups immunized with propranolol. Regarding the analysis of produced cytokines, the groups immunized with ScLL had lower concentrations of cytokines than the non-immunized group, however the ratio of cytokines of the Th1 profile to Th2 was higher. In addition, the animals immunized with peptides and ScLL survived longer than those not immunized, although the difference was not statistically significant. Finally, the parasitic load, when the ScLL group was present, was significantly lower, being around 25% of the load observed in the non-immunized animals. In summary, the results obtained demonstrate that the predicted peptides retained their immunodominant characteristics and, together with ScLL, were able to induce a more effective response against infection, particularly in relation to the chronic phase, thus presenting itself as a potential tool in future prevention studies in the epidemiological chain of toxoplasmosis.
publishDate 2020
dc.date.none.fl_str_mv 2020-03-31
2021-02-18T16:54:09Z
2021-02-18T16:54:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv BARROS, Heber Leão Silva. Avaliação de epítopos derivados de micronema MIC8 e de antígeno de superfície SRS52A de Toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose. 2020. 76 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Uberlândia, Uberlândia, 2020. DOI http://doi.org/10.14393/ufu.te.2020.738.
https://repositorio.ufu.br/handle/123456789/31282
http://doi.org/10.14393/ufu.te.2020.738
identifier_str_mv BARROS, Heber Leão Silva. Avaliação de epítopos derivados de micronema MIC8 e de antígeno de superfície SRS52A de Toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose. 2020. 76 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Uberlândia, Uberlândia, 2020. DOI http://doi.org/10.14393/ufu.te.2020.738.
url https://repositorio.ufu.br/handle/123456789/31282
http://doi.org/10.14393/ufu.te.2020.738
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Imunologia e Parasitologia Aplicadas
publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Imunologia e Parasitologia Aplicadas
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
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instname_str Universidade Federal de Uberlândia (UFU)
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institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
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