Sankaradoss, A and Jagtap, S and Nazir, J and Moula, SE and Modak, A and Fialho, J and Iyer, M and Shastri, JS and Dias, M and Gadepalli, R and Aggarwal, A and Vedpathak, M and Agrawal, S and Pandit, A and Nisheetha, A and Kumar, A and Bordoloi, M and Shafi, M and Shelar, B and Balachandra, SS and Damodar, T and Masika, MM and Mwaura, P and Anzala, O and Muthumani, K and Sowdhamini, R and Medigeshi, GR and Roy, R and Pattabiraman, C and Krishna, S and Sreekumar, E (2022) Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences. In: Molecular Therapy .
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Abstract
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. © 2022 The Authors
| Item Type: | Journal Article |
|---|---|
| Publication: | Molecular Therapy |
| Publisher: | Cell Press |
| Additional Information: | The copyright for this article belongs to Authors |
| Department/Centre: | Division of Mechanical Sciences > Chemical Engineering |
| Date Deposited: | 13 Feb 2022 08:43 |
| Last Modified: | 13 Feb 2022 08:43 |
| URI: | http://eprints.iisc.ac.in/id/eprint/71355 |
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