Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

Lebeau, Grégorie; Lagrave, Alisé; Ogire, Eva; Grondin, Lauriane; S, Seriacaroupin; Moutoussamy, Cédric; Mavingui, Patrick; Hoarau, Jean-Jacques; Roche, Marjolaine; Krejbich-Trotot, Pascale; Desprès, P; Viranaïcken, Wildriss

doi:10.20944/preprints202106.0228.v1

2021

DOI: 10.20944/preprints202106.0228.v1

|View full text |Cite

Preprint

Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

Grégorie Lebeau¹,

Alisé Lagrave²,

Eva Ogire³

et al.

Abstract: Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both ba… Show more

Help me understand this report

View published versions

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2022

2023

Publication Types

Select...

Article4

Relationship

Self Cite1

Independent3

Authors

Journals

Cited by 4 publications

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches

Mukhtar

Wajeeha

Zaidi

et al. 2022

IJMS

View full text Add to dashboard Cite

Dengue virus belonging to the family Flaviviridae and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 cases have been reported, and over 70 lives have been lost. The only commercialized vaccine against DENV, Dengvaxia, cannot be administered as a prophylactic measure to cure this infection due to various complications. Using machine learning and reverse vaccinology approaches, this study was designed to develop a tetravalent modified nucleotide mRNA vaccine using NS1, prM, and EIII sequences of dengue virus from Pakistani isolates. Based on high antigenicity, non-allergenicity, and toxicity profiling, B-cell epitope, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) putative vaccine targets were predicted. Molecular docking confirmed favorable interactions between T-cell epitopes and their respective HLA alleles, while normal mode analysis validated high-affinity interactions of vaccine proteins with immune receptors. In silico immune simulations confirmed adequate immune responses to eliminate the antigen and generate memory. Codon optimization, physicochemical features, nucleotide modifications, and suitable vector availability further ensured better antigen expression and adaptive immune responses. We predict that this vaccine construct may prove to be a good vaccinal candidate against dengue virus in vitro as well.

show abstract

Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches

Mukhtar

Wajeeha

Zaidi

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

Simulation of Hemorrhage Pathogenesis in Mice through Dual Stimulation with Dengue Envelope Protein Domain III-Coated Nanoparticles and Antiplatelet Antibody

Lien

Sun

et al. 2023

IJMS

View full text Add to dashboard Cite

Dengue hemorrhagic fever (DHF) is a severe form of dengue virus (DENV) infection that can lead to abnormal immune responses, endothelial vascular dysfunction, and hemorrhage pathogenesis. The virion-associated envelope protein domain III (EIII) is thought to play a role in the virulence of DENV by damaging endothelial cells. However, it is unclear whether EIII-coated nanoparticles simulating DENV virus particles could cause a more severe pathogenesis than soluble EIII alone. This study aimed to investigate whether EIII-coated silica nanoparticles (EIII-SNPs) could elicit greater cytotoxicity in endothelial cells and hemorrhage pathogenesis in mice compared to EIII or silica nanoparticles alone. The main methods included in vitro assays to assess cytotoxicity and in vivo experiments to examine hemorrhage pathogenesis in mice. EIII-SNPs induced greater endothelial cytotoxicity in vitro than EIII or silica nanoparticles alone. Two-hit combined treatment with EIII-SNPs and antiplatelet antibodies to simulate DHF hemorrhage pathogenesis during secondary DENV infections resulted in higher endothelial cytotoxicity than either treatment alone. In mouse experiments, two-hit combined treatment with EIII-SNPs and antiplatelet antibodies resulted in more severe hemorrhage pathogenesis compared to single treatments of EIII, EIII-SNPs, or antiplatelet antibodies alone. These findings suggest that EIII-coated nanoparticles are more cytotoxic than soluble EIII and could be used to develop a tentative dengue two-hit hemorrhage pathogenesis model in mice. Additionally, our results indicated that EIII-containing DENV particles could potentially exacerbate hemorrhage pathogenesis in DHF patients who have antiplatelet antibodies, highlighting the need for further research on the potential role of EIII in DHF pathogenesis.

show abstract

Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection

Safadi

Lebeau

Lagrave

et al. 2023

Viruses

Self Cite

View full text Add to dashboard Cite

Extracellular vesicles (EVs), produced during viral infections, are of emerging interest in understanding infectious processes and host–pathogen interactions. EVs and exosomes in particular have the natural ability to transport nucleic acids, proteins, and other components of cellular or viral origin. Thus, they participate in intercellular communication, immune responses, and infectious and pathophysiological processes. Some viruses are known to hijack the cell production and content of EVs for their benefit. Here, we investigate whether two pathogenic flaviviruses i.e., Zika Virus (ZIKV) and Dengue virus (DENV2) could have an impact on the features of EVs. The analysis of EVs produced by infected cells allowed us to identify that the non-structural protein 1 (NS1), described as a viral toxin, is associated with exosomes. This observation could be confirmed under conditions of overexpression of recombinant NS1 from each flavivirus. Using different isolation methods (i.e., exosome isolation kit, size exclusion chromatography, Polyethylene Glycol enrichment, and ELISA capture), we showed that NS1 was present as a dimer at the surface of excreted exosomes, and that this association could occur in the extracellular compartment. This finding could be of major importance in a physiological context. Indeed, this capacity of NS1 to address EVs and its implication in the pathophysiology during Dengue or Zika diseases should be explored. Furthermore, exosomes that have demonstrated a natural capacity to vectorize NS1 could serve as useful tools for vaccine development.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

Cited by 4 publications

References 45 publications

Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches

Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches

Simulation of Hemorrhage Pathogenesis in Mice through Dual Stimulation with Dengue Envelope Protein Domain III-Coated Nanoparticles and Antiplatelet Antibody

Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection

Contact Info

Product

Resources

About