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运用免疫信息学方法设计针对新冠病毒和流感病毒同时感染的多表位通用疫苗。

Designing a multi-epitope universal vaccine for concurrent infections of SARS-CoV-2 and influenza viruses using an immunoinformatics approach.

作者信息

Mohammadipour Shirin, Tavakkoli Hadi, Fatemi Seyedeh Narges, Sharifi Aram, Mahmoudi Peyman

机构信息

Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

出版信息

BMC Infect Dis. 2025 May 10;25(1):688. doi: 10.1186/s12879-025-11066-3.

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and influenza viruses share several conserved epitopes that can be utilized for the development of universal vaccines. Our previous research demonstrated that recombinant M2e-HA2 (Matrix-2 ectodomain-Hemagglutinin subunit 2) proteins derived from influenza elicited an immune response against the virus, suggesting their potential use in universal influenza vaccine formulations. Given the lack of a specific vaccine to address SARS‑CoV‑2 and influenza co-infections, this study aimed to design a universal vaccine using immunoinformatics methodologies.

METHODS

In this study, B-cell and T-cell epitopes were identified from the nucleocapsid (N) protein of SARS‑CoV‑2. Additionally, the N-terminal segments of M2e (SLLTEVET) and HA2 (GLFGAIAGF) from influenza were incorporated to construct a multi-epitope vaccine. Suitable linkers were designed, and human beta-defensin-2 was selected as an adjuvant. Further evaluations were conducted, focusing on key parameters such as stability, allergenicity, and antigenicity.

RESULTS

The major histocompatibility complex (MHC) class I and II binding epitopes exhibited broad population coverage for the vaccine on a global scale. The vaccine structure was found to interact with toll-like receptor 3 (TLR-3), and the docked conformation of the vaccine/TLR-3 complex demonstrated high stability during molecular dynamics (MD) simulations. The constructed vaccine exhibited thermal stability across cold, ambient, and human body temperatures. Additionally, in silico cloning of the vaccine candidate into the pET-28a(+) vector was performed to facilitate production within the Escherichia coli expression system.

CONCLUSION

Overall, the findings suggest that the designed vaccine has the potential to serve as an effective universal vaccine and a promising strategy for controlling both Coronavirus disease 2019 (COVID-19) and influenza on a global scale.

摘要

背景

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和流感病毒具有多个保守表位,可用于开发通用疫苗。我们之前的研究表明,源自流感病毒的重组M2e-HA2(基质2外结构域-血凝素亚基2)蛋白可引发针对该病毒的免疫反应,表明其在通用流感疫苗配方中的潜在用途。鉴于缺乏针对SARS-CoV-2和流感合并感染的特异性疫苗,本研究旨在利用免疫信息学方法设计一种通用疫苗。

方法

在本研究中,从SARS-CoV-2的核衣壳(N)蛋白中鉴定出B细胞和T细胞表位。此外,还纳入了来自流感病毒的M2e(SLLTEVET)和HA2(GLFGAIAGF)的N端片段,以构建一种多表位疫苗。设计了合适的连接子,并选择人β-防御素-2作为佐剂。进一步进行了评估,重点关注稳定性、致敏性和抗原性等关键参数。

结果

主要组织相容性复合体(MHC)I类和II类结合表位在全球范围内对该疫苗表现出广泛的人群覆盖。发现该疫苗结构与Toll样受体3(TLR-3)相互作用,并且疫苗/TLR-3复合物的对接构象在分子动力学(MD)模拟过程中显示出高稳定性。构建的疫苗在寒冷、环境和人体温度下均表现出热稳定性。此外,还进行了候选疫苗在pET-28a(+)载体中的电子克隆,以利于在大肠杆菌表达系统中生产。

结论

总体而言,研究结果表明,设计的疫苗有潜力成为一种有效的通用疫苗,是在全球范围内控制2019冠状病毒病(COVID-19)和流感的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7439/12065216/7a0872f2fde1/12879_2025_11066_Fig1_HTML.jpg

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