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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2012.tde-19092012-093646
Document
Author
Full name
Yordanka Medina Armenteros
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Ventura, Armando Morais (President)
Almeida, Maria Elisabete Sbrogio de
Brandão, Paulo Eduardo
Harsi, Charlotte Marianna
Ho, Paulo Lee
Title in Portuguese
Avaliação da resposta imune contra as proteínas L e G do vírus respiratório sincicial humano.
Keywords in Portuguese
Epítopos
Vacinas
Virologia
Vírus de RNA
Abstract in Portuguese
As formulações vacinais contra o Vírus Respiratório Sincicial Humano, HRSV, estão associadas à indução de eosinofilia pulmonar mediada por uma resposta de células TCD4+ Th2, após exposição ao HRSV selvagem. Foi identificado um peptídeo da proteína viral G, que modificado perde a capacidade de predispor à eosinofilia, tornando-o um imunógeno atraente. Células T CD8+ específicas para HRSV reduzem a resposta Th2, mediam resistência a desafio com o vírus, e estão relacionadas à redução dos sintomas. Assim, neste trabalho buscamos e identificamos epítopos de células TCD8+ na polimerase viral, utilizando programas de predição, imunização com peptídeos e avaliação da resposta celular. Também construímos vacinas de DNA contendo a seqüência nucleotídica do peptídeo da proteína G modificado. A caracterização da resposta imune estimulada por essas vacinas e por peptídeos purificados revelou que o plasmídio pTGMCTB, bem como os peptídeos GM e GMCTB, foram capazes de induzir anticorpos que, porém, não se mostraram neutralizantes de HRSV e protetores frente a desafio.
Title in English
Evaluation of the immune response against L and G proteins from human respiratory syncytial virus.
Keywords in English
Epitopes
RNA viruses
Vaccine
Virology
Abstract in English
Vaccines against human respiratory syncytial virus (HRSV) are associated with pulmonary eosinophilia induction mediated by a TCD4+ Th2 response, after exposition to wild HRSV. A peptide from the viral protein G was identified to predispose to eosinophilia and loses this ability when mutated, making it an interesting immunogen. CD8+ T cells specific to HRSV reduce the Th2 response, mediate resistance to virus challenge, and are related to symptom-reduction. Thus, in the present work, we searched for and identified CD8+ T cell epitopes in the viral polymerase; using prediction programs, peptide immunization and evaluation of the cellular response. We also constructed DNA vaccines containing the nucleotide sequence of the mutated peptide from G protein mentioned above. The characterization of the immune response elicited by these vaccines and purified peptides showed that the pTGMCTB plasmid, as well as GM and GMCTB peptides were able to induce antibody response; however they are not neutralizing and protective against HRSV challenge.
 
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Publishing Date
2012-10-23
 
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