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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2016.tde-24022016-114438
Document
Author
Full name
Mariana de Jesus Cintra
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Ferreira, Luis Carlos de Souza (President)
Amaral, Tania Aparecida Tardelli Gomes do
Miyaji, Eliane Namie
Title in Portuguese
Impacto da imunidade prévia nos efeitos adjuvantes da toxina termo-lábil (LT) de Escherichia coli enterotoxigênica.
Keywords in Portuguese
Adjuvantes
Anticorpos
Inflamação
Resposta humoral
Toxina termo-lábil
Abstract in Portuguese
As toxinas LT são expressas por linhagens de Escherichia coli enterotoxigênicas e possuem marcantes efeitos adjuvantes. No entanto, não se conhece se a exposição prévia à toxina afeta sua atividade adjuvante durante imunizações subsequentes. Assim, o presente estudo avaliou o impacto da imunidade pré-existente nas propriedades inflamatórias e adjuvantes da LT quando inoculada pela via subcutânea. Como antígeno modelo, empregou-se a proteína NS1 do vírus dengue e duas abordagens experimentais distintas: (i) incubação in vitro de LT com anticorpos anti-LT e com o receptor gangliosídio (GM1) antes da administração em camundongos não imunizados em conjunto com a proteína NS1 do vírus dengue; (ii) imunização com NS1 coadministrada à LT em camundongos previamente expostos à LT. Foram avaliados os efeitos inflamatórios locais e os efeitos adjuvantes por meio da resposta imunológica humoral anti-NS1. Nossos resultados indicam que a imunidade prévia contra a LT não afeta seu potencial inflamatório e atividade adjuvante. Além disto, a exposição ao receptor GM1 reduziu as reações inflamatórias locais sem, no entanto, reduzir os efeitos adjuvantes de LT.
Title in English
Impact of previous immunity in the adjuvant effects of enterotoxigenic Escherichia coli heat labile toxin (LT).
Keywords in English
Adjuvants
Antibodies
Heat-labile toxin
Humoral response
Inflammation
Abstract in English
LT toxins are expressed by enterotoxigenic Escherichia coli strains and display strong adjuvant effects. Nonetheless, the impact of preexisting immunity on the on LT adjuvant activities is still unknown. Thus, the present study evaluated the impact of pre-existing immunity in the inflammatory and adjuvant properties of LT after subcutaneous administration. the NS1 of dengue virus was employed as a model antigen and two experimental approaches were evaluated: (i) in vitro incubation of LT with LT-specific antibodies and the ganglyoside receptor (GM1) before administration to naïve mice in combination with NS1; (ii) immunization with NS1 co-administered with LT in mice previously exposed to LT. The local inflammatory effects induced by LT were evaluated as wel as the adjuvant effects by means of NS1-specific humoral response. Our results indicate that the LT pre-existing immunity does not affect the inflammatory and adjuvant activities of the toxin. In addition, exposure to GM1 reduced the local inflammatory reactions without affecting the toxin adjuvant effects.
 
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Publishing Date
2016-02-25
 
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