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计算机辅助疫苗设计:靶向D型ε毒素和B型α毒素的高表位区域以实现最佳免疫原性。

In silico vaccine design: Targeting highly epitopic regions of type D epsilon toxin and type B alpha toxin for optimal immunogenicity.

作者信息

Ashoori Nastaran, Ranjbar Mohammad Mehdi, Schirhagl Romana

机构信息

Groningen University, University Medical Centre Groningen, Antonius Deusinglaan 1, 9713AW Groningen, the Netherlands.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

出版信息

Comput Struct Biotechnol J. 2024 Aug 14;25:153-164. doi: 10.1016/j.csbj.2024.08.009. eCollection 2024 Dec.

Abstract

Livestock infections caused by highly toxic bacteria, such as type D and type B, present significant challenges in veterinary medicine. Such infections often require complex and elusive treatment regimens. Developing effective vaccines tailored to combat these specific pathogens remains a pressing need within the field. These bacteria are notorious for their extreme toxicity and the difficulty in culturing them for vaccine production. To address this challenge, we engineered a new potential vaccine candidate capable of neutralizing the virulence of both bacterial strains. Leveraging computational techniques, we identified epitopic regions within Epsilon Toxin (ETX) and Alpha Toxin (ATX). Through fusion gene design, we integrated these epitopic regions alongside the PADRE-peptide sequence. The PADRE-peptide serves as a universal adjuvant to induce an immune response. The culmination of our efforts materialized in a Recombinant Fusion Protein D (rFPD), a novel vaccine construct designed to elicit robust and specific immune defenses against both bacterial species. By combining in-silico design and molecular engineering, our study represents a promising stride toward combating the impact of these pathogenic bacteria in livestock.

摘要

由高毒性细菌(如D型和B型)引起的家畜感染给兽医学带来了重大挑战。此类感染通常需要复杂且难以捉摸的治疗方案。开发针对这些特定病原体的有效疫苗仍是该领域的迫切需求。这些细菌因其极高的毒性以及用于疫苗生产时难以培养而声名狼藉。为应对这一挑战,我们设计了一种新的潜在疫苗候选物,能够中和这两种细菌菌株的毒力。利用计算技术,我们确定了ε毒素(ETX)和α毒素(ATX)中的表位区域。通过融合基因设计,我们将这些表位区域与PADRE肽序列整合在一起。PADRE肽作为一种通用佐剂来诱导免疫反应。我们努力的成果是重组融合蛋白D(rFPD),这是一种新型疫苗构建体,旨在引发针对这两种细菌的强大而特异性的免疫防御。通过结合计算机辅助设计和分子工程,我们的研究朝着对抗这些病原菌对家畜的影响迈出了充满希望的一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e66/11384337/019de87bfef5/ga1.jpg

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