Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences.

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy.

Dengue vaccine development by the year 2020: challenges and prospects.

The first licensed dengue vaccine led to considerable controversy, and to date, no dengue vaccine is in widespread use. All three leading dengue vaccine candidates are live attenuated vaccines, with the main difference between them being the type of backbone and the extent of chimerization. While CYD-TDV (the first licensed dengue vaccine) does not include non-structural proteins of dengue, TAK-003 contains the dengue virus serotype 2 backbone, and the Butantan/Merck vaccine contains three full-genomes of the four dengue virus serotypes. While dengue-primed individuals can already benefit from vaccination against all four serotypes with the first licensed dengue vaccine CYD-TDV, the need for dengue-naive population has not yet been met. To improve tetravalent protection, sequential vaccination should be considered in addition to a heterologous prime-boost approach.