Chan, Yan Qi (2023) Development of tetravalent synthetic peptide dengue vaccine using nanoparticle as vaccine delivery vehicle. Masters thesis, Sunway University.
Full text not available from this repository.Abstract
Dengue is a major public health problem that caused an estimated 390 million infections annually, of which 96 million are symptomatic. Vaccination remains as the major approach in prevention and control of dengue. Only one dengue vaccine [liveattenuated vaccine (LAV), Dengvaxia®] has been licensed for human use but its vaccine efficacy impeded it from serving as an effective universal tetravalent dengue vaccine against all four dengue serotypes. A cost-effective and innovative alternative to LAV is to develop synthetic peptide vaccines which are known for their higher safety profiles due to lack of genetic reversion. Synthetic peptide vaccine is consisted of selected epitope(s) of the antigenic protein which can elicit induction of highly targeted immune responses. In this study, four multi-epitope peptide vaccines (P1-P4) were designed by linking a universal T-Helper epitope (PADRE or TpD) to the highly conserved CD8+ T cell epitope and B cell epitope (B1 or B2) against the four DENV serotypes. However, synthetic peptides suffered from poor immunogenicity and require the use of adjuvants to increase their immunogenicity. Polystyrene nanoparticles (NPs) were used to overcome the poor immunogenicity and dispense with the need for administering toxic adjuvants. The multi-epitope peptides were conjugated to the NPs, creating four multi-epitope peptide-nanoparticle/nanovaccines (NP1-NP4). The vaccine potentials of these four nanovaccines and their respective multi-epitope peptide vaccines were evaluated in BALB/c mice. Mice immunized with polystyrene-based nanovaccines elicited significantly higher titres of IgG and neutralizing antibodies when compared to immunization with multi-epitope peptides only. Immunization with nanovaccines were shown to increase the expression of IFN-γ as determined by ELISPOT, indicating the ability of polystyrene NPs to improve the immunogenicity of multi-epitope peptides even though the CD8+ T cell responses were minimal in intracellular cytokine staining (ICS) assays. Hence, there is a need to screen and replace the CD8+ T cell epitope in the multi-epitope peptide vaccine construct to see if optimal cellular immune response could be induced by different CD8+ T cellepitopes. Among the four polystyrene-based nanovaccines, NP3 which comprised the TpD T-Helper epitope linked to the highly conserved B1 epitope [derived from the envelope (E) protein] held promising potential.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | tetravalent synthetic peptide; dengue vaccine; nanoparticles; synthetic vaccines |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| Divisions: | Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Dept. Biological Sciences |
| Depositing User: | Ms Yong Yee Chan |
| Date Deposited: | 03 Oct 2023 00:36 |
| Last Modified: | 03 Oct 2023 00:36 |
| URI: | http://eprints.sunway.edu.my/id/eprint/2418 |
Actions (login required)
 |
View Item |
