Abstract
Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.
Highlights
Dengue virus (DENV) is a major public health problem especially in the tropical and subtropical regions of the world with approximately 390 million people infected annually [1]
The overall vaccine efficacies in Asia and Latin America were reported to be 56.5% and 64.7%, respectively, the serotype-specific vaccine efficacy in Asia was substantially lower at 50% for serotype 1 and 35% for serotype 2 [13]
Similar trend in serotype-specific vaccine efficacy was reported in the Latin American phase III clinical trial where the efficacies were 50.3% for serotype 1 and 42.3% for serotype 2 [14]
Summary
Dengue virus (DENV) is a major public health problem especially in the tropical and subtropical regions of the world with approximately 390 million people infected annually [1]. The DENV genome is composed of a single, positive-stranded RNA genome of 11 kb that codes for a large polyprotein comprising a capsid protein (C), a membrane protein (M), the major envelope glycoprotein (E) and other non-structural proteins [2]. The E protein is involved in receptor binding of DENV and is the target of neutralising antibodies. The E protein ectodomain consists of three structural domains referred to as domain I (EDI), domain II (EDII), and domain III (EDIII) [3]. EDI is the central domain containing virus-specific cross-reactive epitopes [4]. EDII contains the fusion loop and is involved in dimerization and membrane fusion. The highly conserved fusion loop forms the epicentre of a PLOS ONE | DOI:10.1371/journal.pone.0155900 May 25, 2016
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