Dhaniah Mohamad (2025) Immuno-informatics identification of dengue virus serotype-2 T cell epitopes and their immunological impact on human peripheral blood mononuclear cells. Doctoral thesis, Sunway University.
Full text not available from this repository.Abstract
Dengue fever is a serious worldwide health concern, especially in tropical and subtropical
areas, with 3.6 billion people at risk and approximately 390 million infections reported annually. The dengue virus (DENV) consists of four serotypes: DENV1, DENV2, DENV3, and DENV4. Each has the potential to produce a variety of diseases, ranging from mild dengue fever to severe dengue. Current vaccines, such as Dengvaxia® and Qdenga®, have shown unbalanced efficacy across different serotypes, limiting their overall effectiveness. This study examined the immunogenicity and protective effects of T cell responses against DENV T cell-epitope peptides, particularly against DENV2, the most common serotype among the study participants. Immuno-informatics tools were used to identify potential CD8⁺ and CD4⁺ T cell epitopes specific to DENV. These identified epitopes were then used to construct T cell-epitope peptides that target DENV2. Human peripheral blood mononuclear cells (PBMCs) were isolated from the participants' blood samples and treated with these peptides. To evaluate the T cell immune response, cytokine production was assessed using both the ELISpot assay and intracellular cytokine staining. Flow cytometry was used to identify and quantify T cell subsets, including CD8⁺, CD4⁺, and effector memory T (Tem) cells and evaluated their granulation and proliferation activity using markers, such as CD107a, Ki67, and DNA content. Data from cytokine production, T cell subset analysis, and proliferation activity were statistically analyzed to compare treated and untreated PBMCs and determine the efficacy of DENV2 T cell-epitope peptides. The study found a significant increase in interferon-gamma (IFNγ) production by CD8⁺ and CD4⁺ T cells during the recovery phase, indicating a strong immune response. The frequency of CD8⁺ and CD4⁺ Tem cells also increased, which is important for long-term immunity. The frequency of these Tem cells engaging in proliferation activity was also found to be higher, as indicated by proliferation markers such as Ki67+ and DNA content (DNAlo). There was also an increase in the frequency of effector memory T cells with granulation activity (CD8⁺ CD107a⁺ and CD4⁺ CD107a⁺ Tem cells) that were undergoing proliferation activity. These cells are essential for fighting infected cells because they release cytotoxic granules. The findings highlighted the potential of DENV2 T cell-epitope peptides to elicit strong CD8⁺ and CD4⁺ T cell responses. The observed immune responses were specific to DENV2, indicating a targeted reaction to this serotype. Additionally, there were indications of possible cross reactivity against other DENV serotypes, suggesting that these peptides might offer broader protection beyond just DENV2. These insights are particularly valuable as they enhance the understanding of the host immune response to DENV. Such knowledge is essential for creating dengue prevention and treatment plans that work better. By identifying and utilizing specific T cell-epitope peptides, it may be possible to create vaccines and therapeutic interventions that provide stronger and more comprehensive protection against dengue fever. This study, therefore, contributes significantly to the ongoing efforts to combat this global health concern.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | dengue virus; T cell epitope; CD8+; T cell; CD4+; T cell; immunogenicity |
| Subjects: | Q Science > QR Microbiology > QR355 Virology |
| Divisions: | Sunway University > Faculty of Medical and Life Sciences [formerly School of Medical and Life Sciences until 14 March 2025; School of Healthcare and Medical Sciences until 2020] Sunway University > Faculty of Medical and Life Sciences [formerly School of Medical and Life Sciences until 14 March 2025; School of Healthcare and Medical Sciences until 2020] > Sir Jeffrey Cheah Sunway Medical School > Department of Biomedical Sciences [formerly Dept. Biological Sciences until 21 November 2024] |
| Depositing User: | Ms Yong Yee Chan |
| Date Deposited: | 20 Oct 2026 10:11 |
| Last Modified: | 20 Oct 2026 10:11 |
| URI: | http://repository.sunway.edu.my/id/eprint/3660 |
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