Abstract
BackgroundDengue 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 FindingsSynthetic 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-γ 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.
Highlights
Dengue infections occur in the most of tropical and subtropical areas of the world, and are considered as one of the most important re-emerging disease [1]
Surface accessibility and antigenicity profiles. Parameters such as hydrophilicity, flexibility, accessibility, turns and antigenic propensity of polypeptides chain have been correlated with the location of continuous epitopes. This has led to a search for empirical rules that would allow the position of continuous epitopes to be predicted from certain features of the protein sequence
The evaluation of DENV-3seq, showed that all eleven peptides are in hydrophilic areas according to Kyte and Doolittle hydropathy profiles suggesting that these regions are exposed at the surface of the E protein
Summary
Dengue infections occur in the most of tropical and subtropical areas of the world, and are considered as one of the most important re-emerging disease [1]. The E glycoprotein is the most relevant B-cell antigen, conferring protective immune responses by eliciting neutralizing antibodies and noneutralizing antibodies, which can be involved in enhancement of virus infection. Only few linear immunogenic determinants on the surface of the virion of each dengue serotype have been identified and a detailed map of the dengue linear B-cell epitopes still need to be determined [14]. Most known neutralizing epitopes are conformational, continuous amino acid sequences corresponding to antigenic determinants of the proteins that elicit antibodies in dengue-infected patients are more suitable for protein engineering and vaccine development. 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
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