DENV-Mimetic Polymersome Nanoparticles Bearing Multi-Epitope Lipopeptides Antigen as the Next-Generation Dengue Vaccine

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-e...

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Bibliographic Details
Published in:Pharmaceutics 2022-01, Vol.14 (1), p.156
Main Authors: Abdul Rahman, Nur Adilah, Mohamad Norpi, Abdin Shakirin, Nordin, Muhammad Luqman, Mohd Amin, Mohd Cairul Iqbal, Ahmad Fuaad, Abdullah Al-Hadi, Muhammad Azami, Nor Azila, Marasini, Nirmal, Azmi, Fazren
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Dengue fever
dengue virus
Infections
Lipids
Morphology
multi-epitope
Nanoparticles
peptide vaccine
Peptides
Polymer films
Polymers
polymersome
Proteins
Vaccines
Viruses
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Summary: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-γ 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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14010156