Discovery of B-cell epitopes for development of dengue vaccines and antibody therapeutics

Abstract

Dengue is one of the most frequently transmitted viral infections globally which creates a serious burden to the healthcare system in many countries in the tropical and subtropical regions. To date, no vaccine has demonstrated balanced protection against the four dengue serotypes. Dengvaxia as the only vaccine that has been licensed for use in endemic areas has shown an increased risk in dengue-naïve vaccines to develop severe dengue. A crucial element in protection from dengue infection is the neutralizing antibody responses. Therefore, the identification of protective linear B-cell epitopes can guide vaccine design and facilitate the development of monoclonal antibodies as dengue therapeutics. This review summarizes the identification of dengue B-cell epitopes within the envelope (E) protein of dengue that can be incorporated into peptide vaccine constructs. These epitopes have been identified through approaches such as bioinformatics, three-dimensional structure analysis of antibody-dengue complexes, mutagenesis/alanine scanning and escape mutant studies. Additionally, the therapeutic potential of monoclonal antibodies targeting the E protein of dengue is reviewed. This can provide a basis for the design of future dengue therapies.

Keywords: B-cell epitope; Dengue virus; Envelope glycoprotein; Therapeutic antibody; Vaccine.