A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells

Abstract

Dengue is the most prevalent mosquito-borne viral disease and continues to be a global public health concern. Although a licensed dengue vaccine is available, its efficacy and safety profile are not satisfactory. Hence, there remains a need for a safe and effective dengue vaccine. We are currently developing a bivalent dengue vaccine candidate. This vaccine candidate is composed of a C-terminus truncated non-structural protein 1 (NS1_1-279) and envelope domain III (EDIII) of DENV-2 encapsidated in the nanocarriers, N, N, N-trimethyl chitosan nanoparticles (TMC NPs). The immunogenicity of this bivalent vaccine candidate was investigated in the present study using BALB/c mice. In this work, we demonstrate that NS1 + EDIII TMC NP-immunized mice strongly elicited antigen-specific antibody responses (anti-NS1 and anti-EDIII IgG) and T-cell responses (NS1- and EDIII-specific-CD4⁺ and CD8⁺ T cells). Importantly, the antibody response induced by NS1 + EDIII TMC NPs provided antiviral activities against DENV-2, including serotype-specific neutralization and antibody-mediated complement-dependent cytotoxicity. Moreover, the significant upregulation of Th1- and Th2-associated cytokines, as well as the increased levels of antigen-specific IgG2a and IgG1, indicated a balanced Th1/Th2 response. Collectively, our findings suggest that NS1 + EDIII TMC NPs induced protective responses that can not only neutralize infectious DENV-2 but also eliminate DENV-2-infected cells.

Keywords: Bivalent dengue vaccine; Envelope domain III; N, N, N-trimethyl chitosan; Nanoparticle-based vaccine; Non-structural protein 1.