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基于多病原体的嵌合疫苗以对抗 COVID-19 及其伴随的合并感染。

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections.

机构信息

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Ajmer, Kishangarh, 305817, Rajasthan, India.

Laboratory for Computational Biology & Biomolecular Design, School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi, 221005, Uttar Pradesh, India.

出版信息

Biotechnol Lett. 2023 Jul;45(7):779-797. doi: 10.1007/s10529-023-03380-0. Epub 2023 May 6.

DOI:10.1007/s10529-023-03380-0
PMID:37148345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10163573/
Abstract

BACKGROUND

COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity.

METHODS AND RESULTS

In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis, as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor.

CONCLUSION

The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic.

摘要

背景

COVID-19 已被证明是 2020 年的致命疾病,导致全球数千人死亡,而感染病例仍居高不下。实验研究表明,SARS-CoV-2 与多种微生物相互作用,这种合并感染是导致感染严重程度增加的原因。

方法和结果

在这项研究中,我们通过涉及肺炎链球菌、流感嗜血杆菌和结核分枝杆菌的免疫原性蛋白设计了一种多病原体疫苗,因为它们与 SARS-CoV-2 密切相关。选择了 8 种抗原蛋白序列来预测 B 细胞、HTL 和 CTL 表位,这些表位受最常见的 HLA 等位基因限制。所选表位具有抗原性、非变应原性和非毒性,并与佐剂和接头连接,使疫苗蛋白更具免疫原性、稳定性和灵活性。预测了三级结构、Ramachandran 图和不连续 B 细胞表位。对接和 MD 模拟研究表明,嵌合疫苗与 TLR4 受体具有有效的结合。

结论

三次注射后的细胞因子和 IgG 水平均显示出高水平的免疫模拟分析。因此,这种策略可能是降低疾病严重程度的更好方法,并可作为预防这种大流行的武器。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/765f0376216b/10529_2023_3380_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/6e56970a5c94/10529_2023_3380_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/43db93e90219/10529_2023_3380_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/9986b5bdbe3a/10529_2023_3380_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/ea81890bb8dd/10529_2023_3380_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/fe203e817315/10529_2023_3380_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/765f0376216b/10529_2023_3380_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/6e56970a5c94/10529_2023_3380_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/43db93e90219/10529_2023_3380_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/9986b5bdbe3a/10529_2023_3380_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/ea81890bb8dd/10529_2023_3380_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/fe203e817315/10529_2023_3380_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d42/10163573/765f0376216b/10529_2023_3380_Fig6_HTML.jpg

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