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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2016.tde-17112016-111237
Document
Author
Full name
Lennon Ramos Pereira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Ferreira, Luis Carlos de Souza (President)
Cavalcante, Rafael Ciro Marques
Durigon, Edison Luiz
Salmazi, Karina Inácio Ladislau de Carvalho
Title in Portuguese
Desenvolvimento de formulações vacinais contra a dengue baseadas na proteína não estrutural 1 (NS1) administrada pela via intradérmica.
Keywords in Portuguese
DCIR2
DEC
Dengue
Intradérmico
NS1
Vacina
Abstract in Portuguese
A dengue é uma doença causada pelo vírus da dengue (DENV) cuja incidência é alarmante no mundo. Seu principal método de controle, combate ao vetor, não é totalmente eficaz, o que faz da busca por vacinas seguras e eficazes uma prioridade. Por outro lado o uso de proteínas não estruturais do vírus mostra-se promissor ao desenvolvimento de vacinas contra a dengue. Assim, neste trabalho buscamos desenvolver e caracterizar estratégias vacinais, baseadas na proteína NS1, utilizando a via intradérmica (i.d.) de imunização. Para isso foram obtidas proteínas quimeras contendo a NS1 DENV2 fusionada a anticorpos específicos para os receptores DEC e DCIR2 de células dendríticas. O emprego destas proteínas em ensaios de imunização pelas vias i.d. e i.p induziram respostas humorais NS1-específicas, com modulação do perfil de subclasses de IgG, aumento da afinidade dos mesmos, sem causar efeitos adversos nos animais imunizados. Assim, a inédita combinação da estratégia de direcionamento aqui descrita com a via i.d. faz-se promissora ao desenvolvimento de vacinas contra o DENV.
Title in English
Development of vaccines formulations against dengue based on the nonstructural protein 1 (NS1) administered by the intradermal route.
Keywords in English
DDR2
DEC
Dengue
Intradermal
NS1
Vaccine
Abstract in English
Dengue is a disease caused by dengue virus (DENV) whose incidence is alarming in the world. Its main method of control, combating the vector, is not fully effective, which makes the search for safe and effective vaccines a priority. Moreover the use of non-structural proteins of the virus shows promise for the development of vaccines against dengue. In this work we developed and characterized vaccine strategies based on the NS1 protein using the intradermal route (i.d.) immunization. For this, chimeras containing the NS1 protein fused to DENV2 antibodies specific for the receptor DEC and DCIR2 dendritic cells were obtained. The use of these proteins in immunization trials by way i.d. and i.p. induced NS1-specific humoral responses, with modulation of the IgG subclasses profile, increased affinity thereof without causing adverse effects in the immunized animals. Thus, the new combination of targeting strategy described here with via i.d. any be promising for the development of vaccines against DENV.
 
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Publishing Date
2016-11-17
 
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