Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-08-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2021.1884473 |
| _version_ | 1797674525591076864 |
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| author | Tuksin Jearanaiwitayakul Panya Sunintaboon Runglawan Chawengkittikul Jitra Limthongkul Panuwat Midoeng Preamrudee Chaisuwirat Saradee warit Sukathida Ubol |
| author_facet | Tuksin Jearanaiwitayakul Panya Sunintaboon Runglawan Chawengkittikul Jitra Limthongkul Panuwat Midoeng Preamrudee Chaisuwirat Saradee warit Sukathida Ubol |
| author_sort | Tuksin Jearanaiwitayakul |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T22:00:18Z |
| format | Article |
| id | doaj.art-0b2d882c0f5f483aa36ad2ccfec69250 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:00:18Z |
| publishDate | 2021-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-0b2d882c0f5f483aa36ad2ccfec692502023-09-25T11:13:19ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2021-08-011782793280710.1080/21645515.2021.18844731884473Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo modelsTuksin Jearanaiwitayakul0Panya Sunintaboon1Runglawan Chawengkittikul2Jitra Limthongkul3Panuwat Midoeng4Preamrudee Chaisuwirat5Saradee warit6Sukathida Ubol7Mahidol UniversityMahidol UniversityMahidol UniversityMahidol UniversityPhramongkutklao HospitalPhramongkutklao HospitalNational Science and Technology Development AgencyMahidol UniversityDengue 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.http://dx.doi.org/10.1080/21645515.2021.1884473dengue nanovaccinewhole inactivated dengue virusadjuvant-delivery nanoparticletrimethyl chitosan nanoparticlesimmunogenicity |
| spellingShingle | Tuksin Jearanaiwitayakul Panya Sunintaboon Runglawan Chawengkittikul Jitra Limthongkul Panuwat Midoeng Preamrudee Chaisuwirat Saradee warit Sukathida Ubol Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models Human Vaccines & Immunotherapeutics dengue nanovaccine whole inactivated dengue virus adjuvant-delivery nanoparticle trimethyl chitosan nanoparticles immunogenicity |
| title | Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models |
| title_full | Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models |
| title_fullStr | Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models |
| title_full_unstemmed | Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models |
| title_short | Whole inactivated dengue virus-loaded trimethyl chitosan nanoparticle-based vaccine: immunogenic properties in ex vivo and in vivo models |
| title_sort | whole inactivated dengue virus loaded trimethyl chitosan nanoparticle based vaccine immunogenic properties in ex vivo and in vivo models |
| topic | dengue nanovaccine whole inactivated dengue virus adjuvant-delivery nanoparticle trimethyl chitosan nanoparticles immunogenicity |
| url | http://dx.doi.org/10.1080/21645515.2021.1884473 |
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