Identification of continuous human B-cell epitopes in the envelope glycoprotein of dengue virus type 3 (DENV-3).
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.


RESULTS
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-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively.


CONCLUSIONS
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.
da Silva
Andréa N M Rangel
AN
Virology and Experimental Therapy Laboratory, Aggeu Magalhães Research Center, Fiocruz, Recife, Pernambuco, Brazil.
Nascimento
Eduardo J M
EJ
Cordeiro
Marli Tenório
MT
Gil
Laura H V G
LH
Abath
Frederico G C
FG
Montenegro
Silvia M L
SM
Marques
Ernesto T A
ET
D000818:Animals; D003715:Dengue / Q000276:immunology* / Q000821:virology*; D053059:Dengue Vaccines; D003716:Dengue Virus / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D012372:ROC Curve; D014759:Viral Envelope Proteins / Q000737:chemistry*
D053059:Dengue Vaccines; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins