Lyophilized monkeypox mRNA lipid nanoparticle vaccines with long-term stability and robust immune responses in mice.
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| Název: | Lyophilized monkeypox mRNA lipid nanoparticle vaccines with long-term stability and robust immune responses in mice. |
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| Autoři: | Wang B; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Yin Q; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Yi L; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Su C; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Wen Y; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Qiao M; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Ju Y; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Liu Z; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Xiong Y; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China., Liu Z; Department of Research & Development, Yither Biotech Co Ltd, Shanghai, China. |
| Zdroj: | Human vaccines & immunotherapeutics [Hum Vaccin Immunother] 2025 Dec; Vol. 21 (1), pp. 2477384. Date of Electronic Publication: 2025 Mar 11. |
| Způsob vydávání: | Journal Article |
| Jazyk: | English |
| Informace o časopise: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101572652 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2164-554X (Electronic) Linking ISSN: 21645515 NLM ISO Abbreviation: Hum Vaccin Immunother Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Austin, Tex. : Landes Bioscience |
| Výrazy ze slovníku MeSH: | Nanoparticles*/administration & dosage , Nanoparticles*/chemistry , RNA, Messenger*/immunology , RNA, Messenger*/administration & dosage , RNA, Messenger*/genetics , Mpox, Monkeypox*/prevention & control , Lipids*/administration & dosage , Lipids*/chemistry , Viral Vaccines*/immunology , Viral Vaccines*/administration & dosage, Animals ; Freeze Drying ; Drug Stability ; Mice ; Female ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/genetics ; Antibodies, Viral/blood ; Mice, Inbred BALB C ; Monkeypox virus/immunology ; Monkeypox virus/genetics ; Nanovaccines ; Liposomes |
| Abstrakt: | The World Health Organization (WHO) has recently declared another global health emergency due to the rapidly spreading monkeypox (Mpox) outbreak in numerous African countries. To address the unmet need to contain the outbreak using the existing vaccines, this study developed a lyophilization process for an effective, scalable and affordable Mpox mRNA-LNP vaccine candidate to address the global health crisis. A comprehensive evaluation and optimization of the vaccine formulation (the type/concentration of cryoprotectants, the type/concentration of buffer system, as well as the mRNA concentration and reconstitution solvent) and the freeze-drying process parameters (freezing method, temperature, cooling rate and primary/secondary drying conditions) were conducted. The freeze-dried product exhibits a uniform appearance and a moisture content of less than 1%. Reconstitution of the lyophilized mRNA-LNP resulted in equivalent particle size/polydispersity index, encapsulation efficiency and mRNA integrity compared to that of freshly prepared mRNA-LNP. Furthermore, the lyophilization process can be scaled up 100-fold to 2000 vials/batch. Notably, the lyophilized mRNA-LNP demonstrated a storage stability of at least 12 months at 4°C, and at ambient temperature for a minimum of 8 h post-reconstitution, exhibiting minimal deterioration in product quality. The in vitro biological activity and in vivo immunogenicity of the lyophilized mRNA-LNP was comparable to that of the freshly prepared mRNA-LNP. These results provide a compelling rationale for the utilization of lyophilization technology in enhancing the accessibility of the Mpox mRNA vaccine in developing countries, a strategy that is crucial for containing the global epidemic of Mpox infection. |
| References: | Cell Discov. 2023 Jan 23;9(1):9. (PMID: 36683074) Biophys J. 2006 Apr 15;90(8):2831-42. (PMID: 16443655) Int J Surg. 2022 Aug;104:106745. (PMID: 35777695) Nat Commun. 2023 Sep 22;14(1):5925. (PMID: 37739969) J Pharm Sci. 2021 Mar;110(3):997-1001. (PMID: 33321139) J Control Release. 2023 May;357:149-160. (PMID: 36958400) Pharm Res. 2004 Feb;21(2):191-200. (PMID: 15032301) Mol Ther. 2022 May 4;30(5):1941-1951. (PMID: 35131437) Int J Pharm. 2024 Jan 25;650:123688. (PMID: 38070660) Int J Surg. 2022 Aug;104:106812. (PMID: 35944803) Bioact Mater. 2020 Mar 18;5(2):358-363. (PMID: 32206737) Mol Ther Nucleic Acids. 2022 Dec 13;30:226-240. (PMID: 36187052) Front Microbiol. 2023 May 05;14:1160984. (PMID: 37213509) Signal Transduct Target Ther. 2023 Apr 28;8(1):172. (PMID: 37117161) Chem Soc Rev. 2018 Sep 17;47(18):7116-7139. (PMID: 30137078) Biochim Biophys Acta. 1994 Jul 13;1193(1):143-50. (PMID: 8038184) Eur J Pharm Biopharm. 2009 Feb;71(2):181-9. (PMID: 18940256) Biotechnol Adv. 2020 May - Jun;40:107534. (PMID: 32088327) Travel Med Infect Dis. 2023 Mar-Apr;52:102550. (PMID: 36754340) Travel Med Infect Dis. 2024 Mar-Apr;58:102694. (PMID: 38336336) Pharmaceutics. 2018 Aug 28;10(3):. (PMID: 30154315) Saudi Med J. 2024 Aug;45(9):1002-1003. (PMID: 39218470) Int J Surg. 2022 Sep;105:106873. (PMID: 36055631) J Pharm Sci. 2017 Jul;106(7):1706-1721. (PMID: 28341598) Ann Anat. 2025 Feb;258:152366. (PMID: 39631569) J Pharm Sci. 2011 Jul;100(7):2935-44. (PMID: 21328583) Expert Opin Drug Deliv. 2011 Mar;8(3):375-88. (PMID: 21294603) Eur J Pharm Sci. 2010 Nov 20;41(3-4):546-55. (PMID: 20800680) Int J Pharm. 2021 May 15;601:120586. (PMID: 33839230) J Pharm Sci. 2004 Sep;93(9):2259-73. (PMID: 15295787) Eur J Pharm Biopharm. 2021 Aug;165:345-360. (PMID: 34052428) Vaccines (Basel). 2024 Apr 05;12(4):. (PMID: 38675767) New Microbes New Infect. 2022 Nov 15;49-50:101049. (PMID: 36407851) Int J Pharm. 2024 Sep 5;662:124514. (PMID: 39067550) Adv Mater. 2023 Jun;35(26):e2211420. (PMID: 36972555) Biotechnol Prog. 2010 May-Jun;26(3):727-33. (PMID: 20039442) Cell. 2024 Mar 14;187(6):1363-1373.e12. (PMID: 38366591) Int J Surg. 2022 Aug;104:106774. (PMID: 35863624) J Control Release. 2024 Sep;373:952-961. (PMID: 39067793) Biomater Sci. 2023 Jun 13;11(12):4327-4334. (PMID: 37073472) Travel Med Infect Dis. 2022 Sep-Oct;49:102392. (PMID: 35752293) Biomed Pharmacother. 2023 Nov;167:115597. (PMID: 37783148) |
| Contributed Indexing: | Keywords: Monkeypox; batch consistency; long-term stability; lyophilized mRNA vaccines; scalability |
| Substance Nomenclature: | 0 (RNA, Messenger) 0 (Vaccines, Synthetic) 0 (Lipids) 0 (Antibodies, Viral) 0 (Viral Vaccines) 0 (Lipid Nanoparticles) 0 (Nanovaccines) 0 (Liposomes) |
| Entry Date(s): | Date Created: 20250311 Date Completed: 20250512 Latest Revision: 20250512 |
| Update Code: | 20250513 |
| PubMed Central ID: | PMC11901372 |
| DOI: | 10.1080/21645515.2025.2477384 |
| PMID: | 40066621 |
| Databáze: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | The World Health Organization (WHO) has recently declared another global health emergency due to the rapidly spreading monkeypox (Mpox) outbreak in numerous African countries. To address the unmet need to contain the outbreak using the existing vaccines, this study developed a lyophilization process for an effective, scalable and affordable Mpox mRNA-LNP vaccine candidate to address the global health crisis. A comprehensive evaluation and optimization of the vaccine formulation (the type/concentration of cryoprotectants, the type/concentration of buffer system, as well as the mRNA concentration and reconstitution solvent) and the freeze-drying process parameters (freezing method, temperature, cooling rate and primary/secondary drying conditions) were conducted. The freeze-dried product exhibits a uniform appearance and a moisture content of less than 1%. Reconstitution of the lyophilized mRNA-LNP resulted in equivalent particle size/polydispersity index, encapsulation efficiency and mRNA integrity compared to that of freshly prepared mRNA-LNP. Furthermore, the lyophilization process can be scaled up 100-fold to 2000 vials/batch. Notably, the lyophilized mRNA-LNP demonstrated a storage stability of at least 12 months at 4°C, and at ambient temperature for a minimum of 8 h post-reconstitution, exhibiting minimal deterioration in product quality. The in vitro biological activity and in vivo immunogenicity of the lyophilized mRNA-LNP was comparable to that of the freshly prepared mRNA-LNP. These results provide a compelling rationale for the utilization of lyophilization technology in enhancing the accessibility of the Mpox mRNA vaccine in developing countries, a strategy that is crucial for containing the global epidemic of Mpox infection. |
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| ISSN: | 2164-554X |
| DOI: | 10.1080/21645515.2025.2477384 |