Article
Identification of continuous human B-cell epitopes in the envelope glycoprotein of dengue virus type 3 (DENV-3)
Registro en:
SILVA, A. N. M. R. da et al. Identification of continuous human B-cell epitopes in the envelope glycoprotein of dengue virus type 3 (DENV-3). PloS One, v. 4, n. 10, p. 1-9, 13 Oct. 2009.
1932-6203
10.1371/journal.pone.0007425
Autor
Silva, Andréa N. M. Rangel da
Nascimento, Eduardo J. M.
Cordeiro, Marli Tenório
Gil, Laura H. V. G.
Abath, Frederico Guilherme Coutinho
Montenegro, Silvia M. L.
Marques, Ernesto T. A.
Resumen
O trabalho contou com o apoio do Ministério da Saúde, do programa FIOCRUZ-PDTIS RVR 09, do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) e do Instituto Nacional de Saúde dos Estados Unidos (NIH) concedidos no U19 AI05641. A SML Montenegro é beneficiária de bolsas do CNPq. Os financiadores não tiveram nenhum papel no desenho do estudo, coleta e análise de dados, decisão de publicar ou preparação do manuscrito. Uma patente (PI0704650-2) foi solicitada para os epítopos apresentados neste manuscrito. Background: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes.
Methodology/Principal Findings: Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51–65, 71–90, 131–170, 196–210 and 246–260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51–65), 27 and 28 (aa131–150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51–65, 131–170, 196–210 and 246–260 elicited the highest antibody response and epitopes131–170, 196–210 and 246–260, elicited IFN-c production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. Conclusions/Significance: Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine.
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