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

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.