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针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的新型自扩增信使核糖核酸（mRNA）疫苗脂质纳米颗粒的免疫信息学

Immunoinformatic of novel self-amplifying mRNA vaccine lipid nanoparticle against SARS-CoV-2.

作者信息

Fath Turmidzi, Bachtiar Endang Winiati, Alitongbieke Gulimiran, Pan Yutian, Hu Yuanqing, Widowati Retno

机构信息

Engineering Technological Center of Mushroom Industry, Minnan Normal University, Zhangzhou, Fujian 363000, China.

Department of Biology, Faculty of Biology, Universitas Nasional, Jakarta, Indonesia.

出版信息

J Adv Pharm Technol Res. 2024 Apr-Jun;15(2):91-98. doi: 10.4103/JAPTR.JAPTR_424_23. Epub 2024 May 6.

DOI:10.4103/JAPTR.JAPTR_424_23
PMID:38903554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11186542/
Abstract

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.

摘要

我们基于S蛋白和Nsp3蛋白的衍生物开发了创新的自扩增mRNA（sa-mRNA）疫苗，这些蛋白被认为对粘附人类宿主细胞至关重要。我们进行了与KK和GPGPG接头融合的B细胞、主要组织相容性复合体（MHC）I类和II类表位分析。我们还在疫苗结构中纳入了5'帽序列、科扎克序列、复制酶序列、3'/5'非翻译区和聚腺苷酸尾。随后对接疫苗结构，并与TLR7分子进行分子动力学模拟。作为免疫反应模拟的结果，在二次和三次剂量时，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IgG-1同种型的免疫反应急剧加速，提高了10倍以上，而自然杀伤细胞、巨噬细胞和树突状细胞在首次给药后显示出相对较高的浓度。根据我们的发现，IgM+IgG、IgG1+IgG2和IgM水平（由sa-mRNA疫苗诱导）在第25天和第50天增加了两倍，随后在第70-150天下降了三倍。然而，在150-350天内，其水平持续保持在20000-21000的范围内。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/0268f2052869/JAPTR-15-91-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/c285121b0ae2/JAPTR-15-91-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/b24ccc7f3ec8/JAPTR-15-91-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/1eb24ef575ab/JAPTR-15-91-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/6544d937a5d5/JAPTR-15-91-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/6a9e4e309c87/JAPTR-15-91-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/9ced251f0544/JAPTR-15-91-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/c9720594f50d/JAPTR-15-91-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/173a2a5218b6/JAPTR-15-91-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/0268f2052869/JAPTR-15-91-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/c285121b0ae2/JAPTR-15-91-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/b24ccc7f3ec8/JAPTR-15-91-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/1eb24ef575ab/JAPTR-15-91-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/6544d937a5d5/JAPTR-15-91-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/6a9e4e309c87/JAPTR-15-91-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/9ced251f0544/JAPTR-15-91-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/c9720594f50d/JAPTR-15-91-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/173a2a5218b6/JAPTR-15-91-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9d/11186542/0268f2052869/JAPTR-15-91-g009.jpg

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