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Nanodelivery system enhances the immunogenicity of dengue-2 nonstructural protein 1, DENV-2 NS1

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dc.contributor.authorTuksin Jearanaiwitayakulen_US
dc.contributor.authorPanya Sunintaboonen_US
dc.contributor.authorRunglawan Chawengkittikulen_US
dc.contributor.authorJitra Limthongkulen_US
dc.contributor.authorPanuwat Midoengen_US
dc.contributor.authorSaradee wariten_US
dc.contributor.authorSukathida Ubolen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherThailand National Center for Genetic Engineering and Biotechnologyen_US
dc.contributor.otherPhramongkutklao College of Medicineen_US
dc.date.accessioned2020-10-05T03:55:18Z
dc.date.available2020-10-05T03:55:18Z
dc.date.issued2020-10-07en_US
dc.description.abstract© 2020 Elsevier Ltd Nonstructural protein 1 (NS1) of dengue virus (DENV) is currently recognized as a dengue vaccine candidate. Unfortunately, most of non-replicating immunogens typically stimulate unsatisfactory immune responses, thus, the additional adjuvant is required. In this study, C-terminal truncated DENV-2 NS1 loaded in N,N,N, trimethyl chitosan nanoparticles (NS11-279TMC NPs) was prepared through the ionic gelation method. The immunogenicity of NS11-279TMC NPs was investigated using human ex vivo as well as the murine model. Through a human ex vivo model, it was demonstrated in this study that not only can TMC particles effectively deliver NS11-279 protein into monocyte-derived dendritic cells (MoDCs), but also potently stimulate those cells, resulting in increased expression of maturation marker (CD83), costimulating molecules (CD80, CD86 and HLA-DR) and markedly secreted various types of innate immune cytokines/chemokines. Moreover, mice administered with NS11-279TMC NPs strongly elicited both antibody and T cell responses, produced higher levels of IgG, IgG1, IgG2a and potently activated CD8+ T cells, as compared to mice administered with soluble NS11-279. Importantly, we further demonstrated that anti-NS11-279 antibody induced by this platform of NS11-279 effectively eliminated DENV-2 infected cells through antibody dependent complement-mediated cytotoxicity. Significantly, anti-DENV2 NS11-279 antibody exerted cross-antiviral activity against DENV-1 and −4 but not against DENV-3 infected cells. These findings demonstrate that TMC exerts a desirable adjuvant for enhancing delivery and antigenicity of NS1 based dengue vaccine.en_US
dc.identifier.citationVaccine. Vol.38, No.43 (2020), 6814-6825en_US
dc.identifier.doi10.1016/j.vaccine.2020.08.021en_US
dc.identifier.issn18732518en_US
dc.identifier.issn0264410Xen_US
dc.identifier.other2-s2.0-85089598963en_US
dc.identifier.urihttps://hdl.handle.net/20.500.14594/58948
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089598963&origin=inwarden_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.subjectMedicineen_US
dc.titleNanodelivery system enhances the immunogenicity of dengue-2 nonstructural protein 1, DENV-2 NS1en_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089598963&origin=inwarden_US
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