| Texto completo | |
| Autor(es): |
Almeida, Rafael Ribeiro
[1, 2]
;
Raposo, Rui Andre Saraiva
[3]
;
Coirada, Fernanda Caroline
[1]
;
da Silva, Jamile Ramos
[4]
;
de Souza Ferreira, Luis Carlos
[4]
;
Kalil, Jorge
[5, 1, 2]
;
Nixon, Douglas F.
[3]
;
Cunha-Neto, Edecio
[5, 1, 2]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Div Clin Immunol & Allergy, Dept Med, Sao Paulo - Brazil
[2] Inst Invest Immunol INCT, Sao Paulo - Brazil
[3] George Washington Univ, Dept microbiol Immunol & Trop Med, Washington, DC - USA
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil
[5] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Immunology and Cell Biology; v. 93, n. 10, p. 868-876, NOV 2015. |
| Citações Web of Science: | 3 |
| Resumo | |
DNA vaccines have failed to induce satisfactory immune responses in humans. Several mechanisms of double-stranded DNA (dsDNA) sensing have been described, and modulate DNA vaccine immunogenicity at many levels. We hypothesized that the immunogenicity of DNA vaccines in humans is suppressed by APOBEC (apolipoprotein B (APOB) mRNA-editing, catalytic polypeptide)-mediated plasmid degradation. We showed that plasmid sensing via STING (stimulator of interferon (IFN) genes) and TBK-1 (TANK-binding kinase 1) leads to IFN-beta induction, which results in APOBEC3A mRNA upregulation through a mechanism involving protein kinase C signaling. We also showed that murine APOBEC2 expression in HEK293T cells led to a 10-fold reduction in intracellular plasmid levels and plasmid-encoded mRNA, and a 2.6-fold reduction in GFP-expressing cells. A bicistronic DNA vaccine expressing an immunogen and an APOBEC2-specific shRNA efficiently silenced APOBEC2 both in vitro and in vivo, increasing the frequency of induced IFN-gamma-secreting T cells. Our study brings new insights into the intracellular machinery involved in dsDNA sensing and how to modulate it to improve DNA vaccine immunogenicity in humans. (AU) | |
| Processo FAPESP: | 08/57881-0 - Instituto de investigacao em imunologia |
| Beneficiário: | Jorge Elias Kalil Filho |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 06/50096-0 - Characterization of human immunodeficiency virus type 1 (hiv-1) in a cohort of recently infected persons from the state of sao paulo by full genome sequencing. |
| Beneficiário: | Sabri Saeed Mohammed Ahmed Al-Sanabani |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 04/15856-9 - Analise prospectiva das caracteristicas virologicas e imunologicas em individuos com infeccao recente pelo hiv-1 das cidades de sao paulo e santos, sp. |
| Beneficiário: | Ricardo Sobhie Diaz |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |