Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models

ABSTRACT

Dengue virus (DENV) is a mosquito-borne virus that poses an incomparable public health problem, particularly in tropical and subtropical areas. Vaccination remains the most rational measure for controlling DENV infection. In this study, an ultraviolet irradiation (UV)-inactivated DENV-2 carried by N,N,N-trimethyl chitosan nanoparticles (UV-inactivated DENV2 TMC NPs) was investigated as a potential non-replicating dengue vaccine candidate. Using a human ex vivo model, the human monocyte-derived dendritic cells (MoDCs), we showed that TMC served as both a vaccine vehicle and a potent adjuvant. TMC NPs not only efficiently enhanced UV-inactivated DENV2 internalization into MoDCs but also greatly increased the breadth of UV-inactivated DENV2 immunogenicity to drive the maturation of MoDCs. Moreover, UV-inactivated DENV2 TMC NPs were highly immunogenic in mice, inducing greater levels of antibodies (total IgG, IgG1, IgG2a and neutralizing antibodies) and T cells (activated CD4⁺ and CD8⁺ T cells) against DENV-2 compared to soluble DENV-2 immunogens. Notably, the neutralizing activity of sera from mice immunized with UV-inactivated DENV2 TMC NPs was significantly augmented in the presence of complement activation, leading to the strong elimination of both DENV-2 particles and infected cells. We further showed that the immunogenicity of an inactivated dengue-based vaccine was significantly improved in a concentration-dependent manner. These positive results warrant further investigations of this platform of vaccine delivery for tetravalent vaccines or monovalent vaccines in sequential immunizations.

KEYWORDS:

• Dengue nanovaccine
• whole inactivated dengue virus
• adjuvant-delivery nanoparticle
• trimethyl chitosan nanoparticles
• immunogenicity

Acknowledgments

We would like to acknowledge Miss Suthikarn Apichirapokey and Miss Mathurin Seesen for their technical assistance.

Disclosure of potential conflicts of interest

The authors declare that there are no competing financial interests or personal relationships that could affect the work reported in this paper.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the National Vaccine Institute, Thailand [2558.1/7] to Ubol S. and Royal Golden Jubilee (RGJ) Ph.D. Programme [PHD/0018/2558] to Jearanaiwitayakul T. from Thailand Science Research and Innovation (TSRI).