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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2009.tde-03022010-090935
Document
Author
Full name
Adriana Leticia Goldoni
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Sato, Maria Notomi (President)
Aoki, Valeria
Arruda, Luciana Barros de
Carbonare, Solange Barros
Ventura, Armando Morais
Title in Portuguese
Estudo da imunogenicidade da vacina de DNA quimérica LAMP/gag do HIV-1 em sítios de mucosa de camundongos imunizados no período neonatal.
Keywords in Portuguese
DNA
HIV
Imunologia
Mucosa
Neonatologia
Vacinas
Abstract in Portuguese
O desenvolvimento de vacinas imunogênicas em mucosas é essencial na prevenção da infecção pelo HIV. A vacina LAMP/gag associa o gene LAMP murino com o gene gag do HIV-1, possibilitando a apresentação antigênica no contexto das moléculas de classe II do MHC. Os resultados mostraram que a imunização com vacina quimérica LAMP/gag induziu produção de anticorpos sIgA e IgG anti-GAG e associação das vias intrasanal e intradérmica possibilitou a geração de resposta humoral de mucosa e sistêmica anti-GAG. Ambas as vacinas LAMP/gag e gag induziram resposta de células T CD8+ similares. Entretanto, a resposta T CD4+ foi mais pronunciada nos animais LAMP/gag, que reconheceram o dobro do número de pools de peptídeos da GAG e aumento da SFC de IFN-g e IL-4. A associação do adjuvante ODN CpG A às vacinas regulou negativamente a resposta medida por células T CD4+ e a produção de anticorpos IgG2a. Os dados evidenciaram que apenas a vacina quimérica LAMP/gag foi capaz de induzir resposta imune celular e humoral e memória imunológica, por ativar mais eficazmente as células T CD4+.
Title in English
Immunogenicity study of the HIV LAMP/gag chimera DNA vaccine in the mucosa sites of immunized mice during neonatal phase.
Keywords in English
DNA
HIV
Immunology
Mucosa
Neonatology
Vaccines
Abstract in English
The development of mucosal immunogenic vaccines is essential to prevent HIV infection. The LAMP/gag vaccine strategy associates the murine LAMP gene and the HIV-1 gag gene, allowing antigenic presentation in the context of MHC class II molecules. The results showed that the immunization with LAMP/gag chimera DNA vaccine induced anti-GAG sIgA and IgG antibodies and the association of intradermal injection to the intranasal immunization protocol induced anti-GAG antibodies. Both LAMP/gag and gag vaccines generated a strong CD8+ T-cell response. However, the CD4+ T cells response was more pronounced in LAMP/gag mice, able to recognized twice the number of GAG peptide pools and increasing the amplitude of IFN-g and IL-4 SFC. The association of the CpG ODN adjuvant to the DNA vaccines downregulated the CD4+ T cells response and the IgG2a antibodies production. The data showed that only the LAMP/gag chimera DNA vaccine was able of inducing cellular and humoral immune responses and immunological memory due to the adequate CD4+ T cells activation.
 
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Publishing Date
2010-03-04
 
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