DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine

Abdul Rahman, Nur Adilah and Mohamad Norpi, Abdin Shakirin and Nordin, Muhammad Luqman and Mohd Amin, Mohd Cairul Iqbal and Ahmad Fuaad, Abdullah Al-Hadi and Muhammad Azami, Nor Azila and Marasini, Nirmal and Azmi, Fazren (2022) DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine. Pharmaceutics, 14 (1). ISSN 1999-4923, DOI https://doi.org/10.3390/pharmaceutics14010156.

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Abstract

Dengue remains a severe threat to public health. The safety and efficacy of the licensed dengue vaccine is not clinically satisfactory, which necessitate the need of new approach in designing an effective dengue vaccine without eliciting adverse reaction. Herein, we have designed a lipidated multi-epitope peptide vaccine (LipoDV) that can elicit highly targeted humoral and cell-mediated immune responses. To improve its immunogenicity, LipoDV was presented on the surface of MPLA-functionalized polymersome nanoparticles (PNs-LipoDV-MPLA). The as-constructed vaccine delivery platform resembles the structural morphology of DENV owing to its spherical nanoscale particle size and surface immunostimulatory properties given by LipoDV and MPLA that emulating the functional role of DENV E and prM/M proteins respectively. A proof-of-concept study demonstrated that BALB/c mice immunized with PNs-LipoDV-MPLA induced a stronger antigen-specific antibody response with an enhanced cell-mediated immunity as characterized by the elevated IFN-gamma secretion in comparison to other tested vaccine candidates which possess a lesser structural trait of DENV. The DENV-mimicking nanoparticles vaccine exhibited negligible toxicity as analyzed by hemolytic test, MTT assay, histopathological examination and abnormal toxicity test on immunized mice. Collectively, our study provides a strong foundation in designing an effective peptide-based vaccine delivery platform against DENV infection.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Multi-epitope;Peptide vaccine;Nanoparticles; dengue virus; Polymersome
Subjects: R Medicine
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 04 Aug 2022 08:06
Last Modified: 04 Aug 2022 08:06
URI: http://eprints.um.edu.my/id/eprint/33511

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