Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa
Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cell...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/179841 |
| _version_ | 1826124573919150080 |
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| author | Benetti, Ayça Altay Tan, Eugene Yang Zhi Chang, Zi Wei Bae, Ki Hyun Thwin, Ma Thinzar Muthuramalingam, Ram Pravin Kumar Liao, Kuo-Chieh Wan, Yue Ng, Lisa F. P. Renia, Laurent Liu, Jianping Chen, Xiaoyuan Yang, Yi Yan White, Kevin P. Pastorin, Giorgia |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Benetti, Ayça Altay Tan, Eugene Yang Zhi Chang, Zi Wei Bae, Ki Hyun Thwin, Ma Thinzar Muthuramalingam, Ram Pravin Kumar Liao, Kuo-Chieh Wan, Yue Ng, Lisa F. P. Renia, Laurent Liu, Jianping Chen, Xiaoyuan Yang, Yi Yan White, Kevin P. Pastorin, Giorgia |
| author_sort | Benetti, Ayça Altay |
| collection | NTU |
| description | Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies. |
| first_indexed | 2024-10-01T06:22:55Z |
| format | Journal Article |
| id | ntu-10356/179841 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:22:55Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1798412024-09-01T15:38:10Z Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa Benetti, Ayça Altay Tan, Eugene Yang Zhi Chang, Zi Wei Bae, Ki Hyun Thwin, Ma Thinzar Muthuramalingam, Ram Pravin Kumar Liao, Kuo-Chieh Wan, Yue Ng, Lisa F. P. Renia, Laurent Liu, Jianping Chen, Xiaoyuan Yang, Yi Yan White, Kevin P. Pastorin, Giorgia Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences A*STAR Infectious Diseases Labs Medicine, Health and Life Sciences Vaccines Liposomes Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies. Published version This research was funded by Prepare GRANT, grant number A-8001420-00-00. 2024-08-27T05:22:37Z 2024-08-27T05:22:37Z 2024 Journal Article Benetti, A. A., Tan, E. Y. Z., Chang, Z. W., Bae, K. H., Thwin, M. T., Muthuramalingam, R. P. K., Liao, K., Wan, Y., Ng, L. F. P., Renia, L., Liu, J., Chen, X., Yang, Y. Y., White, K. P. & Pastorin, G. (2024). Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa. Vaccines, 12(4), 409-. https://dx.doi.org/10.3390/vaccines12040409 2076-393X https://hdl.handle.net/10356/179841 10.3390/vaccines12040409 38675792 2-s2.0-85191721112 4 12 409 en Vaccines © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Vaccines Liposomes Benetti, Ayça Altay Tan, Eugene Yang Zhi Chang, Zi Wei Bae, Ki Hyun Thwin, Ma Thinzar Muthuramalingam, Ram Pravin Kumar Liao, Kuo-Chieh Wan, Yue Ng, Lisa F. P. Renia, Laurent Liu, Jianping Chen, Xiaoyuan Yang, Yi Yan White, Kevin P. Pastorin, Giorgia Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa |
| title | Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa |
| title_full | Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa |
| title_fullStr | Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa |
| title_full_unstemmed | Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa |
| title_short | Design and characterization of a new formulation for the delivery of COVID-19-mRNA vaccine to the nasal mucosa |
| title_sort | design and characterization of a new formulation for the delivery of covid 19 mrna vaccine to the nasal mucosa |
| topic | Medicine, Health and Life Sciences Vaccines Liposomes |
| url | https://hdl.handle.net/10356/179841 |
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