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

Antibodies, Neutralizing Antibodies, Viral COVID-19 Dengue / prevention & control Dengue Vaccines / genetics Dengue Virus / genetics Humans Pandemics Vaccines, DNA Viral Envelope Proteins / genetics

DNA vaccine EDIII domain NS1 protein antibody-dependent enhancement consensus sequence dengue dengue surveillance

Journal

Molecular therapy : the journal of the American Society of Gene Therapy

ISSN: 1525-0024

Titre abrégé: Mol Ther

Pays: United States

ID NLM: 100890581

Informations de publication

Date de publication:
04 05 2022

Historique:

received: 02 11 2021

revised: 24 12 2021

accepted: 05 01 2022

pubmed: 10 1 2022

medline: 10 5 2022

entrez: 9 1 2022

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ymthe.2022.01.013 PMID: 34999210 PMC: PMC8736276

pubmed: 34999210

pii: S1525-0016(22)00013-2

doi: 10.1016/j.ymthe.2022.01.013

pmc: PMC8736276

pii:

doi:

Substances chimiques

Antibodies, Neutralizing 0

Antibodies, Viral 0

Dengue Vaccines 0

Vaccines, DNA 0

Viral Envelope Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2058-2077

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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