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Master's Dissertation
DOI
https://doi.org/10.11606/D.87.2016.tde-24082016-100639
Document
Author
Full name
Pamela Siumey Liu
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Dias, Waldely de Oliveira (President)
Amaral, Tania Aparecida Tardelli Gomes do
Takagi, Mickie
Title in Portuguese
Resposta imune induzida em camundongos por imunização transcutânea com proteína recombinante LipL32 de leptospira.
Keywords in Portuguese
Leptospira
LipL32
Monofosforil lipídeo A
Polietilenoglicol
Surfactante pulmonar
Vacinas
Abstract in Portuguese
A imunização transcutânea (TCI) é uma via atrativa para o desenvolvimento de vacinação livre de agulhas, atuando nas APCs da pele, podendo substituir algumas das imunizações convencionais, em termos de facilidade, segurança e eficácia. O presente estudo avaliou a resposta imune da TCI com proteína recombinante de leptospira LipL32, uma proteína altamente conservada em cepas patogênicas e potente candidata vacinal. A TCI com a LipL32 na região abdominal de C57BL-6 foi capaz de primar o sistema imune, suscitando resposta sistêmica com altos níveis de anticorpos contra o antígeno, após reforços subimunizantes, ID e Tc. O padrão de citocinas em cultivo de células do sangue total dos grupos imunizados indicou que a imunização Tc foi capaz de primar o sistema imune, tanto inato quanto adaptativo. O tratamento local ou a coadministração com surfactantes ou PEG não evidenciou ação emoliente ou adjuvante. A coadministração Tc da LipL32 com MPL-A levou a efeito moderador da reação pro-inflamatória, redirecionando a resposta adaptativa, tanto humoral quanto celular.
Title in English
Immune response induced in mice by transcutaneous immunization with recombinant protein LipL32 of leptospira.
Keywords in English
Leptospira
LipL32
Monophosphoryl lipid A
Polyethylene glycol
Pulmonary surfactant
Vaccines
Abstract in English
Transcutaneous immunization (TCI) offers an attractive pathway for the development of needle-free vaccination by acting on APCs of the skin, showing potential to replace conventional immunization, in terms of safety and efficacy. In this study we evaluated the immune response by TCI with recombinant protein of leptospira LipL32, a highly conserved protein among pathogenic strains, a potential vaccine candidate. TCI with LipL32 was evaluated in C57BL-6 mice abdominal region and was able to confer systemic response with high levels of antibodies after subimmunizing ID and Tc boosters. The pattern of cytokines in cell cultures from whole blood of immunized groups indicated that the TCI was able to prime the immune system, for both innate and adaptive response. Local treatment of the skin or coadministration with surfactants and PEG did not show an emollient and an adjuvant action. Co-administration of LipL32 with MPL-A influenced the antibody response as well as showed a moderating effect of the pro-inflammatory reaction, redirecting the adaptive response.
 
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Publishing Date
2016-08-24
 
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