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Previous issue date: 2006-12-05 / Control of human visceral leishmaniasis in endemic regions is hampered in part by the lack of knowledge with respect of the role reservoirs and vector. In addition, there is not yet an understanding of how non-symptomatic subclinical infection might influence the maintenance of infection in a particular locality. Of worrisome is the limited accessibility to medical care in places with emerging drug resistance. There is still no available protective vaccine either for humans or other reservoirs. Leishmania species are protozoa that express multiple antigens which are recognized by the vertebrate immune system. Since there is not one immunodominant epitope recognized by most hosts, strategies must be developed to optimize selection of antigens for prevention and immunodiagnosis. For this reason, we generated a cDNA library from the intracellular amastigote form of Leishmania chagasi, the causative agent of South American visceral leishmaniasis. We employed a two-step expression screen of the library to systematically identify T and T-dependent B cell antigens. The first step was aimed at identifying the largest possible number of clones producing an epitope-containing polypeptide with a pool of sera from Brazilians with documented visceral leishmaniasis. After removal of clones encoding heat shock proteins, positive clones underwent a second step screen for their ability to cause proliferation and IFN-γ responses of T cells from immune mice. Six unique clones were selected from the second screen for further analysis. The clones encoded part of the coding sequence of glutamine synthetase, transitional endoplasmic reticulum ATPase, elongation factor 1γ, kinesin K-39, repetitive protein A2, and a hypothetical conserved protein. Humans naturally infected with L. chagasi mounted both cellular and antibody responses to these protein Preparations containing multiple antigens may be optimal for immunodiagnosis and protective vaccines against Leishmania / O controle da Leishmaniose Visceral em regi?es end?micas ? em parte dificultado pela falta de conhecimento em rela??o ao papel dos reservat?rios e vetores, n?o havendo ainda vacina dispon?vel. Leishmania s.p s?o protozo?rios que expressam m?ltiplos ant?genos reconhecidos pelo sistema imune dos hospedeiros. Devido ? aus?ncia de um ep?topo imunodominante reconhecido pela maioria dos hospedeiros, estrat?gias para a identifica??o e sele??o de novos ant?genos para a preven??o e imunodiagn?stico. Nossa estrat?gia foi construir uma biblioteca de cDNA da forma amastigota da L. chagasi, com subseq?ente realizad??o de dupla varredura da biblioteca para sistematicamente identificar ant?genos espec?ficos de c?lulas T e B. A primeira etapa teve como objetivo a identifica??o do maior n?mero de clones produtores de pept?deos atrav?s da utiliza??o de um pool de soro de indiv?duos com Leishmaniose Visceral. Os clones codificadores de prote?nas de choque t?rmico foram removidos e os clones restantes foram submetidos ? segunda etapa da varredura, que consistiu na avali??o capacidade destes ant?genos em induzir estimula??o e prolifera??a de linf?citos T de camundongos resistentes ? infec??o por L. chagasi. Seis clones foram selecionados ap?s a segunda varredura. Os clones codificaram parte da seq??ncia da glutamina sintetase, ATPase do ret?culo endoplasm?tico, Fator de alongamento 1 γ, Kinesina K-39 prote?na repetitiva A2, e prote?na hipot?tica conservada. Indiv?duos naturalmente infectados com L. chagasi desenvolveram respostas imunes celular e humoral frente a essas prote?nas. Formula??es contendo m?ltiplos ant?genos podem servir como excelentes m?todos para imunodiagn?stico e vacina??o
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13112 |
| Date | 05 December 2006 |
| Creators | Salha, Daniella Regina Arantes Martins |
| Contributors | CPF:15603016434, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785584A3&dataRevisao=null, Carvalho, Lain Pontes, CPF:34745866704, http://lattes.cnpq.br/6148007775748893, Pompeu, Margarida Maria de Lima, CPF:11779420382, http://lattes.cnpq.br/2618502430533433, Santos, Elizeu Antunes dos, CPF:41305655400, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782221T9&dataRevisao=null, Braz, Regina de F?tima dos Santos, CPF:00567556867, http://lattes.cnpq.br/9442000157600332, Jer?nimo, Selma Maria Bezerra |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Ci?ncias da Sa?de, UFRN, BR, Ci?ncias da Sa?de |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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