Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models
| Autor: | Runglawan Chawengkittikul, Sukathida Ubol, Jitra Limthongkul, Saradee Warit, Panya Sunintaboon, Tuksin Jearanaiwitayakul, Panuwat Midoeng, Preamrudee Chaisuwirat |
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| Rok vydání: | 2021 |
| Předmět: |
viruses
medicine.medical_treatment 030231 tropical medicine Immunology Dengue Vaccines Dengue virus Antibodies Viral medicine.disease_cause Virus Dengue Mice 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals Immunology and Allergy 030212 general & internal medicine Dengue vaccine Pharmacology Chitosan Chemistry Immunogenicity Dengue Virus Antibodies Neutralizing Virology Vaccination Vaccines Inactivated Nanoparticles Adjuvant Ex vivo Research Paper |
| Zdroj: | Hum Vaccin Immunother |
| ISSN: | 2164-554X 2164-5515 |
| DOI: | 10.1080/21645515.2021.1884473 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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