利用反向疫苗学和免疫信息学方法从乙型肝炎病毒HBc和HBx蛋白中设计基于多表位的治疗性候选疫苗

IF 2.6 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
PLoS ONE Pub Date : 2024-12-06 eCollection Date: 2024-01-01 DOI:10.1371/journal.pone.0313269
Patricia Gita Naully, Marselina Irasonia Tan, Husna Nugrahapraja, Aluicia Anita Artarini, Reza Aditama, Ernawati Arifin Giri-Rachman
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引用次数: 0

摘要

慢性乙型肝炎(CHB)病例的主要问题是患者的免疫反应无法消除乙型肝炎病毒(HBV)的共价闭合环状DNA (cccDNA)小染色体。涉及HBV核心蛋白(HBc)和HBV X蛋白(HBx)的表观遗传调控影响cccDNA小染色体的转录和稳定性。已开发的基于HBc和/或hbx的治疗性疫苗不能适应HBV基因型之间的差异。本研究旨在利用反向疫苗学(RV)和免疫信息学方法设计一种基于HBc和HBx多表位的治疗性候选疫苗。从NCBI Entrez Protein数据库中获得10种HBV基因型的HBc和HBx序列。结果表明,共有13610条HBc序列和12333条HBx序列预测表位。该研究确定了4个细胞毒性T淋巴细胞表位,2个辅助T淋巴细胞表位和5个线性B淋巴细胞符合纳入标准。使用霍乱毒素亚基B和泛HLA dr结合表位佐剂设计的候选疫苗预计是安全的、抗原性的、稳定的,全球人口覆盖率为99.43%。分子对接和分子动力学模拟表明,该候选疫苗能够稳定地与B细胞受体、细胞毒性T细胞受体和TLR4结合100 ns。免疫反应模拟表明,它可以诱导抗体的产生和B细胞和T细胞的增殖。由此可见,RV和免疫信息学成功地促进了乙肝多表位治疗性候选疫苗的设计。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Design of multi-epitope-based therapeutic vaccine candidates from HBc and HBx proteins of hepatitis B virus using reverse vaccinology and immunoinformatics approaches.

Design of multi-epitope-based therapeutic vaccine candidates from HBc and HBx proteins of hepatitis B virus using reverse vaccinology and immunoinformatics approaches.

Design of multi-epitope-based therapeutic vaccine candidates from HBc and HBx proteins of hepatitis B virus using reverse vaccinology and immunoinformatics approaches.

Design of multi-epitope-based therapeutic vaccine candidates from HBc and HBx proteins of hepatitis B virus using reverse vaccinology and immunoinformatics approaches.

The major problem in cases of chronic hepatitis B (CHB) is the failure of the patient's immune response to eliminate the covalently closed circular DNA (cccDNA) minichromosome of hepatitis B virus (HBV). Epigenetic regulation involving the HBV core protein (HBc) and HBV X protein (HBx) influences the transcription and stability of the cccDNA minichromosome. The HBc and/or HBx-based therapeutic vaccines that have been developed cannot accommodate differences between HBV genotypes. This research aims to design a therapeutic vaccine candidate based on the multi-epitope of HBc and HBx using reverse vaccinology (RV) and immunoinformatics approach. HBc and HBx sequences from 10 HBV genotypes were obtained from the NCBI Entrez Protein database. Epitopes were predicted from consensus sequences, which consisted of 13,610 HBc sequences and 12,333 HBx sequences. The study identified four cytotoxic T lymphocyte epitopes, two helper T lymphocyte epitopes, and five linear B lymphocyte that met the inclusion criteria. The vaccine candidate designed using cholera toxin subunit B and pan HLA DR-binding epitope adjuvants was predicted to be safe, antigenic, stable, and has a global population coverage of 99.43%. Molecular docking and molecular dynamics simulations demonstrated that the vaccine candidate could stably bind to B cell receptor, cytotoxic T cell receptor, and TLR4 for 100 ns. Immune response simulation indicated that it can induce antibody production and the proliferation of B and T cells. It can be concluded that RV and immunoinformatics successfully facilitated the design of a multi-epitope therapeutic vaccine candidate for CHB.

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来源期刊
PLoS ONE
PLoS ONE 生物-生物学
CiteScore
6.20
自引率
5.40%
发文量
14242
审稿时长
3.7 months
期刊介绍: PLOS ONE is an international, peer-reviewed, open-access, online publication. PLOS ONE welcomes reports on primary research from any scientific discipline. It provides: * Open-access—freely accessible online, authors retain copyright * Fast publication times * Peer review by expert, practicing researchers * Post-publication tools to indicate quality and impact * Community-based dialogue on articles * Worldwide media coverage
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