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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my.um.eprints.335112022-08-04T08:06:29Z http://eprints.um.edu.my/33511/ DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine 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 R Medicine RM Therapeutics. Pharmacology RS Pharmacy and materia medica 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. MDPI 2022-01 Article PeerReviewed 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 <https://doi.org/10.3390/pharmaceutics14010156>. 10.3390/pharmaceutics14010156 |
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R Medicine RM Therapeutics. Pharmacology RS Pharmacy and materia medica 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 DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
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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. |
format |
Article |
author |
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 |
author_facet |
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 |
author_sort |
Abdul Rahman, Nur Adilah |
title |
DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
title_short |
DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
title_full |
DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
title_fullStr |
DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
title_full_unstemmed |
DENV-Mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
title_sort |
denv-mimetic polymersome nanoparticles bearing multi-epitope lipopeptides antigen as the next-generation dengue vaccine |
publisher |
MDPI |
publishDate |
2022 |
url |
http://eprints.um.edu.my/33511/ |
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1740826038131228672 |
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13.160551 |