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Advancing PEDV Vaccination: Comparison between Inactivated and Flagellin N-Terminus-Adjuvanted Subunit Vaccines.

ABSTRACT: Vaccinations can serve as an important preventive measure against the porcine epidemic diarrhea (PED) virus that currently threatens the swine industry. This study focuses on the development of a fusion protein vaccine, FliC₉₉-mCOE, which combines the N-terminus of flagellin (FliC₉₉) with a modified core neutralizing epitope (mCOE) of PEDV. In silico immunoinformatic analysis confirmed the construct's non-toxic, non-allergenic, and highly antigenic nature. Molecular docking and molecular dynamics (MD) simulations demonstrated FliC₉₉-mCOE's strong binding to the TLR-5 immunological receptor. Repeated exposure simulations and immunological simulations suggested enhanced cell-mediated immunity. Both FliC₉₉-mCOE and an inactivated PEDV vaccine were produced and tested in mice. The results from cell proliferation, ELISA, and neutralization assays indicated that FliC₉₉-mCOE effectively stimulated cellular immunity and neutralized PEDV. We conclude that the FliC₉₉-mCOE fusion protein may serve as a promising vaccine candidate against PEDV.

SUBMITTER: Murtaza A

PROVIDER: S-EPMC10892538 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Advancing PEDV Vaccination: Comparison between Inactivated and Flagellin N-Terminus-Adjuvanted Subunit Vaccines.

Murtaza Asad A Hoa Nguyen-Thanh NT Dieu-Huong Do D Afzal Haroon H Tariq Muhammad Hamza MH Cheng Li-Ting LT Chung Yao-Chi YC

Vaccines 20240129 2

Vaccinations can serve as an important preventive measure against the porcine epidemic diarrhea (PED) virus that currently threatens the swine industry. This study focuses on the development of a fusion protein vaccine, FliC99-mCOE, which combines the N-terminus of flagellin (FliC99) with a modified core neutralizing epitope (mCOE) of PEDV. In silico immunoinformatic analysis confirmed the construct's non-toxic, non-allergenic, and highly antigenic nature. Mol ...[more]

PMID: 38400123

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Project description:BackgroundThe newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL.MethodsUsing a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective.ResultsAt a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy.ConclusionsA strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Dataset Information

Advancing PEDV Vaccination: Comparison between Inactivated and Flagellin N-Terminus-Adjuvanted Subunit Vaccines.

Publications

Advancing PEDV Vaccination: Comparison between Inactivated and Flagellin N-Terminus-Adjuvanted Subunit Vaccines.

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