Heng, Wen Tzuen * (2024) Development of a multi-epitope Influenza A vaccine with self-adjuvanting Poly-Laticco-Glycolic Acid (PLGA) delivery. Masters thesis, Sunway University.
Full text not available from this repository.Abstract
Influenza is a highly contagious respiratory disease led to 3-5 million severe cases worldwide, resulting in over 650,000 respiratory deaths annually. To date, the efficacy of the seasonal influenza vaccines were estimated to be only 29% against the circulating influenza B/Victoria and A(H1N1)pdm2009. This highlighted the need to develop a next generation influenza vaccine that could induce long-lasting and cross-reactive immunity in vaccinated individuals. Many strategies have been explored for the development of next-generation influenza vaccines and the multi-epitope peptide-based vaccine is one of the promising vaccine platforms as they are cost-effective, easily modifiable, and have minimal risk of reactogenicity. However, the multi-epitope peptide based vaccines often required to be incorporated with adjuvant to increase their immunogenicity. In this study, the immunogenicity of each of the ten peptides derived from literature mining was validated in BALBC/c mice by incorporating them in different peptide formulations containing adjuvant components such as Montanide ISA 51, complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA) containing CpG ODN 1826. Prior to in vivo study, the ten peptides selected from literature mining were subjected to immunoinformatic analysis. Subsequently, immunization of mice with the respective peptide formulations showed that mice immunized with the mixture of ten peptides formulated in IFA containing CpG ODN 1826 elicited the strongest cell-mediated immune responses in the immunised mice than that observed in mice immunized with the mixture of ten peptides formulated in CFA, highlighting that the incorporation of CpG ODN 1826 produced a synergistic effect when formulated in IFA as an adjuvant. Importantly, a total of six immunogenic peptides (M2.1, M2.2, NP, P3, P5 and P6) were identified as they were shown to stimulate significant IFN-! production in immune cells as well as CD4+ and CD8+ T-cells. Recently, nanoparticles emerged as a potential delivery platform for protein or peptide based vaccines. As such, the FDA-approved poly (D, L-lactide-co-glycolic acid) (PLGA) was used to encapsulate the mixture of six immunogenic peptides to be evaluated as a nanovaccine and its immunogenicity was evaluated and compared to the mixture of six peptides formulated in IFA containing CpG ODN 1826 in BALB/c mice. Remarkably, mice immunized with PLGA NPs encapsulating six peptides elicited the strongest IgG response at 1,000,000 titres and it was ten-fold higher when compared to mice immunized with the mixture of six peptides formulated in IFA containing CpG ODN 1826. In addition, immunization of mice with PLGA NPs incapsulating the six peptides was shown to increase the expression of IFN-! significantly (2-3-fold higher) when compared with the group of mice administered with the mixture of six peptides formulated in IFA containing CpG ODN 1826. However, one of the peptides, P3, was found to induce a significant necrotic effect in the CD3+ T-cells present in murine splenocytes. Elimination of peptide 3 from the current nanovaccine formulation would be ideal in future studies. Overall, the study demonstrated the self-adjuvanting property of the PLGA nanoparticles as a delivery system without the need to include any toxic and costly conventional adjuvants in the multi-epitope peptide-based vaccine.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | adjuvant; multi-epitope; nanoparticle; next-generation influenza vaccine; PLGA nanoparticle. |
| 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] |
| Depositing User: | Ms Yong Yee Chan |
| Related URLs: | |
| Date Deposited: | 29 Jul 2025 05:44 |
| Last Modified: | 29 Jul 2025 05:44 |
| URI: | http://eprints.sunway.edu.my/id/eprint/3244 |
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