{"title":"新型自扩增 mRNA 疫苗脂质纳米颗粒对 SARS-CoV-2 的免疫表型。","authors":"Turmidzi Fath, Endang Winiati Bachtiar, Gulimiran Alitongbieke, Yutian Pan, Yuanqing Hu, Retno Widowati","doi":"10.4103/JAPTR.JAPTR_424_23","DOIUrl":null,"url":null,"abstract":"<p><p>We developed innovative self-amplifying mRNA (sa-mRNA) vaccine based on the derivative of S and Nsp3 proteins, which are considered crucial adhering to human host cells. We performed B-cell, Major histocompatibility complex (MHC) I, and II epitope which were merged with the KK and GPGPG linker. We also incorporated 5' cap sequence, Kozak sequence, replicase sequence, 3'/5' UTR, and poly A tail within the vaccine structure. The vaccine structure was subsequently docked and run the molecular dynamic simulation with TLR7 molecules. As the results of immune response simulation, the immune response was accelerated drastically up to >10-fold for immunoglobulin, interferon-γ, interleukin-2, immunoglobulin M (IgM) + immunoglobulin G (IgG) isotype, IgM isotype, and IgG1 isotype in secondary and tertiary dose, whereas natural killer cells, macrophages, and dendritic cells showed relatively high concentrations after the first dose. As our finding, the IgM + IgG, IgG1 + IgG2, and IgM level (induced by sa-mRNA vaccine) ensued three times with two-fold increase in days 25, and 50, then decreased after days 70-150. However, 150-350 days demonstrated constantly in the range of 20,000-21,000.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186542/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immunoinformatic of novel self-amplifying mRNA vaccine lipid nanoparticle against SARS-CoV-2.\",\"authors\":\"Turmidzi Fath, Endang Winiati Bachtiar, Gulimiran Alitongbieke, Yutian Pan, Yuanqing Hu, Retno Widowati\",\"doi\":\"10.4103/JAPTR.JAPTR_424_23\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We developed innovative self-amplifying mRNA (sa-mRNA) vaccine based on the derivative of S and Nsp3 proteins, which are considered crucial adhering to human host cells. We performed B-cell, Major histocompatibility complex (MHC) I, and II epitope which were merged with the KK and GPGPG linker. We also incorporated 5' cap sequence, Kozak sequence, replicase sequence, 3'/5' UTR, and poly A tail within the vaccine structure. The vaccine structure was subsequently docked and run the molecular dynamic simulation with TLR7 molecules. As the results of immune response simulation, the immune response was accelerated drastically up to >10-fold for immunoglobulin, interferon-γ, interleukin-2, immunoglobulin M (IgM) + immunoglobulin G (IgG) isotype, IgM isotype, and IgG1 isotype in secondary and tertiary dose, whereas natural killer cells, macrophages, and dendritic cells showed relatively high concentrations after the first dose. As our finding, the IgM + IgG, IgG1 + IgG2, and IgM level (induced by sa-mRNA vaccine) ensued three times with two-fold increase in days 25, and 50, then decreased after days 70-150. However, 150-350 days demonstrated constantly in the range of 20,000-21,000.</p>\",\"PeriodicalId\":14877,\"journal\":{\"name\":\"Journal of Advanced Pharmaceutical Technology & Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186542/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Advanced Pharmaceutical Technology & Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4103/JAPTR.JAPTR_424_23\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Advanced Pharmaceutical Technology & Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/JAPTR.JAPTR_424_23","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
摘要
我们开发了基于 S 和 Nsp3 蛋白衍生物的创新型自扩增 mRNA(sa-mRNA)疫苗。我们将 B 细胞、主要组织相容性复合体(MHC)I 和 II 表位与 KK 和 GPGPG 连接器合并。我们还在疫苗结构中加入了 5' cap 序列、Kozak 序列、复制酶序列、3'/5' UTR 和 poly A 尾部。随后,我们将疫苗结构与 TLR7 分子对接并进行分子动力学模拟。免疫反应模拟结果显示,免疫球蛋白、干扰素-γ、白细胞介素-2、免疫球蛋白M(IgM)+免疫球蛋白G(IgG)同种型、IgM同种型和IgG1同种型的免疫反应在第二和第三剂量时急剧加速,最高可达10倍以上,而自然杀伤细胞、巨噬细胞和树突状细胞在第一剂量后表现出相对较高的浓度。根据我们的研究结果,IgM + IgG、IgG1 + IgG2 和 IgM 水平(由 sa-mRNA 疫苗诱导)随之出现了三次变化,在第 25 和 50 天增加了两倍,然后在第 70-150 天后下降。然而,在 150-350 天内,IgG 水平一直在 20,000-21,000 之间。
Immunoinformatic of novel self-amplifying mRNA vaccine lipid nanoparticle against SARS-CoV-2.
We developed innovative self-amplifying mRNA (sa-mRNA) vaccine based on the derivative of S and Nsp3 proteins, which are considered crucial adhering to human host cells. We performed B-cell, Major histocompatibility complex (MHC) I, and II epitope which were merged with the KK and GPGPG linker. We also incorporated 5' cap sequence, Kozak sequence, replicase sequence, 3'/5' UTR, and poly A tail within the vaccine structure. The vaccine structure was subsequently docked and run the molecular dynamic simulation with TLR7 molecules. As the results of immune response simulation, the immune response was accelerated drastically up to >10-fold for immunoglobulin, interferon-γ, interleukin-2, immunoglobulin M (IgM) + immunoglobulin G (IgG) isotype, IgM isotype, and IgG1 isotype in secondary and tertiary dose, whereas natural killer cells, macrophages, and dendritic cells showed relatively high concentrations after the first dose. As our finding, the IgM + IgG, IgG1 + IgG2, and IgM level (induced by sa-mRNA vaccine) ensued three times with two-fold increase in days 25, and 50, then decreased after days 70-150. However, 150-350 days demonstrated constantly in the range of 20,000-21,000.
期刊介绍:
Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is an Official Publication of Society of Pharmaceutical Education & Research™. It is an international journal published Quarterly. Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is available in online and print version. It is a peer reviewed journal aiming to communicate high quality original research work, reviews, short communications, case report, Ethics Forum, Education Forum and Letter to editor that contribute significantly to further the scientific knowledge related to the field of Pharmacy i.e. Pharmaceutics, Pharmacology, Pharmacognosy, Pharmaceutical Chemistry. Articles with timely interest and newer research concepts will be given more preference.