Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences [C-CAMP Bioincubation Facility]

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TitleImmune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences [C-CAMP Bioincubation Facility]
Publication TypeJournal Article
Year of Publication2022
AuthorsSankaradoss A, Jagtap S, Nazir J, Moula SE, 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
JournalMolecular Therapy - Cell Press
Date Published2022 Jan 07
Type of ArticleJournal Article
ISSN1525-0024
Keywordsantibody-dependent enhancement, consensus sequence, dengue, dengue surveillance, DNA vaccine, EDIII domain, NS1 protein
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.

URLhttps://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(22)00013-2#secsectitle0165
DOI10.1016/j.ymthe.2022.01.013
Alternate JournalMol Ther
PubMed ID34999210
PubMed Central IDPMC8736276