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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2012.tde-03082012-083441
Document
Author
Full name
Hugo Rezende Henriques
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Boscardin, Silvia Beatriz (President)
Bordignon, Juliano
Rosa, Daniela Santoro
Title in Portuguese
Análise das respostas adaptativas quando um antígeno do vírus da dengue é direcionado para duas populações distintas de células dendríticas.
Keywords in Portuguese
Camundongos
Células dendríticas
Dengue
Sistema imune
Vacinas
Abstract in Portuguese
Células dendríticas são importantes na interação dos sistemas imune inato e adaptativo, apresentando antígenos para linfócitos T CD4+ e CD8+ e induzindo respostas adaptativas contra estes. Elas são alvo de interesse no desenvolvimento de novas estratégias vacinais que visam o direcionamento de antígenos para as diferentes populações de DCs in vivo. Consiste na administração de anticorpos contra receptores da superfície da DC em fusão com o antígeno. Nós comparamos o direcionamento da proteína NS1 de DENV2 para as duas principais populações de DCs no baço, na presença de diferentes agonistas. Poly I:C é capaz de induzir as respostas de Linfócitos T CD8+ mais robustas, mas somente quando o antígeno é direcionado para a população de DCs CD8+DEC205+. Com CpG observamos resposta de células T CD8+ equivalente quando a proteína foi direcionada para qualquer uma das populações estudadas. Direcionamento com Poly I:C gerou proteção contra desafio por DENV2 quando NS1 é direcionada para a população de DCs DEC205+, sendo esta proteção dependente de Linfócitos T CD8+ e CD4+.
Title in English
Analysis of the adaptive immune responses when a dengue virus antigen is targeted to two distinct populations of dendritic cells.
Keywords in English
Dendritic cells
Dengue
Immune system
Mice
Vaccines
Abstract in English
Dendritic Cells are critical in the interaction between innate and the adaptive immune system, presenting antigens to T lymphocytes and inducing adaptive immune responses against these. DCs are target for development of new vaccine strategies based on targeting antigens to different DCs populations in vivo. This consists on the administration of antibodies specific to DC surface endocytic receptor fused to an antigen. In this study, we evaluated the differences in adaptive responses when the NS1 protein from the DENV2 was directed to the two main populations of DCs in the spleen along with different agonistic molecules. Highest CD8+ T cell responses were seen when Poly I:C was used, but only when directed to the CD8+DEC205+ DC population. In the presence of agonist CpG we observed similar responses when the protein was targeted to either CD8+DEC205+ or CD8-DCIR2+ DCs. In the presence of Poly I:C, only targeting to the DEC205+ DCs was able to protect mice against a challenge with DENV2. This protection was dependent on both CD8+ and CD4+ T cell responses.
 
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Publishing Date
2012-08-16
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • HENRIQUES, Hugo Rezende, et al. Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge [doi:10.1371/journal.pntd.0002330]. PLoS Neglected Tropical Diseases [online], 2013, vol. 7, n. 7, p. e2330.
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