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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2014.tde-15122014-125225
Document
Author
Full name
Camila Mathias dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Ferreira, Luis Carlos de Souza (President)
Guth, Beatriz Ernestina Cabilio
Martinez, Marina Baquerizo
Miyaji, Eliane Namie
Soares, Irene da Silva
Title in Portuguese
Toxinas termo-lábeis (LTs) do tipo II de Escherichia coli enterotoxigênica (ETEC): efeito adjuvante e atividade inflamatória.
Keywords in Portuguese
Escherichia coli enterotoxigênica
Adjuvantes imunológicos
Toxinas bacterianas
Toxinas termo-lábeis
Vacinas
Abstract in Portuguese
Este trabalho realizou importantes avanços na elucidação do potencial das toxinas termo-lábeis do tipo II (LT-IIs) como adjuvantes por via intradérmica e transcutânea. Os dados gerados indicam que LT-IIb e LT-IIc nativas atuam como potentes adjuvantes vacinais por via intradérmica induzindo respostas imunológicas antígeno específicas, como medido pela produção de anticorpos sistêmicos (IgG) e ativação de linfócitos T CD8+ citotóxicos. Soma-se ao potencial adjuvante demonstrado para as LT-IIs por essa via a baixa reatogenicidade das moléculas, com menores níveis de edema e reduzida migração leucocitária para o sítio de inoculação em comparação a LT-I. Os resultados indicam também que o efeito adjuvante das LTs aplicadas por via transcutânea pode estar relacionado à capacidade de ligação ao gangliosídeo GM1 já que a toxina LT-IIb, incapaz de interagir com este receptor, não apresenta efeito adjuvante por essa via. O conjunto de dados apresentados abre perspectivas para o emprego das LT-IIs nativas como adjuvantes parenterais em vacinas para animais e humanos.
Title in English
Type II heat-labile toxins (LTs) from enterotoxigenic Escherichia coli (ETEC): adjuvant effect and inflammatory activity.
Keywords in English
Bacterial toxins
Enterotoxigenic Escherichia coli
Heat-labile toxins
Immunological adjuvants
Vaccines
Abstract in English
This work has made significant advances in the understanding of the potential of type II heat-labile toxins (LT-IIs) as vaccine adjuvants by intradermal and transcutaneous route. The generated data indicate that native forms of LT-IIb and LT-IIc act as potent vaccine adjuvants when intradermally injected inducing antigen-specific immune responses, as measured by the generation of systemic serum antibody (IgG) and activation of cytotoxic CD8+ T lymphocytes. Besides the adjuvant effects, LT-IIs show reduced side effects, measured by the lesser edema formation and reduced leukocytes migration to the site of injection, in comparison to LT-I. The results also indicate that the adjuvant activity of LTs applied transcutaneously may be related to the the ganglioside GM1 binding property since the LT-IIb toxin, unable to interact with this receptor, has no adjuvant effect by this route. The presented data set opens prospects for the employment of native LT-IIs as parenteral adjuvants in vaccines for animals and humans.
 
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Publishing Date
2014-12-16
 
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