Journal
VACCINE
Volume 38, Issue 43, Pages 6814-6825Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2020.08.021
Keywords
DENV NS1(1-279); Adjuvant-delivery nanoparticle; Trimethyl chitosan nanoparticles
Categories
Funding
- National Vaccine Institute, Thailand [2558.1/7]
- Thailand Science Research and Innovation (TSRI) [PHD/0018/2558]
Ask authors/readers for more resources
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 (NS1(1-279) TMC NPs) was prepared through the ionic gelation method. The immunogenicity of NS1(1-279) TMC 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 NS1(1-279) 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 NS1(1-279) TMC 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 NS1(1-279). Importantly, we further demonstrated that anti-NS1(1-279) antibody induced by this platform of NS1(1-279) effectively eliminated DENV-2 infected cells through antibody dependent complement-mediated cytotoxicity. Significantly, anti-DENV2 NS1(1-279) 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. (C) 2020 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available