Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences.
|Title||Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Sankaradoss A, Jagtap S, Nazir J, Moula S-E, Modak A, Fialho J, Iyer M, Shastri JS, Dias M, Gadepalli R, Aggarwal A, Vedpathak M, Agrawal S, Pandit A, Nisheetha A, Kumar A, Bordoloi M, Shafi M, Shelar B, Balachandra SS, Damodar T, Masika MMuia, Mwaura P, Anzala O, Muthumani K, Sowdhamini R, Medigeshi GR, Roy R, Pattabiraman C, Krishna S, Sreekumar E|
|Date Published||2022 Jan 06|
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 DENV-2 NS1 protein coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on 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. Vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying of intracellular IFN-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios and immune gene profiling suggest a strong Th1-dominant immune response. Finally, 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; offering a novel vaccine candidate with a possible broad spectrum protection and successful clinical translation either as a stand-alone or in a mix and match strategy.
|Alternate Journal||Mol Ther|