Publication: Nanodelivery system enhances the immunogenicity of dengue-2 nonstructural protein 1, DENV-2 NS1
Issued Date
2020-10-07
Resource Type
ISSN
18732518
0264410X
0264410X
Other identifier(s)
2-s2.0-85089598963
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Mahidol University
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SCOPUS
Bibliographic Citation
Vaccine. Vol.38, No.43 (2020), 6814-6825
Suggested Citation
Tuksin Jearanaiwitayakul, Panya Sunintaboon, Runglawan Chawengkittikul, Jitra Limthongkul, Panuwat Midoeng, Saradee warit, Sukathida Ubol Nanodelivery system enhances the immunogenicity of dengue-2 nonstructural protein 1, DENV-2 NS1. Vaccine. Vol.38, No.43 (2020), 6814-6825. doi:10.1016/j.vaccine.2020.08.021 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/58948
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Title
Nanodelivery system enhances the immunogenicity of dengue-2 nonstructural protein 1, DENV-2 NS1
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.