Area Inmunología, DEPBIO/IQB, Facultad de Química/Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay; Graduate Program in Chemistry, Facultad de Química, Universidad de la Republica, Uruguay.
Area Inmunología, DEPBIO/IQB, Facultad de Química/Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay.
Biologicals. 2023 May;82:101684. doi: 10.1016/j.biologicals.2023.101684. Epub 2023 May 16.
Vaccines are among the most important advances in medicine throughout the human history. However, conventional vaccines exhibit several drawbacks in terms of design and production costs. Peptide-based vaccines are attractive alternatives, since they can be designed mainly in silico, can be produced cheaply and safely, and are able to induce immune responses exclusively towards protective epitopes. Yet, a proper peptide design is needed, not only to generate peptide-specific immune responses, but also for them to recognize the native protein in the occurrence of a natural infection. Herein, we propose a rational workflow for developing peptide-based vaccines including novel steps that assure the cross-recognition of native proteins. In this regard, we increased the probability of generating efficient antibodies through the selection of linear B-cell epitopes free of post-translational modifications followed by analyzing the 3D-structure similarity between the peptide in-solution vs. within its parental native protein. As a proof of concept, this workflow was applied to a set of seven previously suggested potential protective antigens against the infection by Echinococcus granulosus sensu lato. Finally, two peptides were obtained showing the capacity to induce specific antibodies able to exert anti-parasite activities in different in vitro settings, as well as to provide significant protection in the murine model of secondary echinococcosis.
疫苗是人类历史上医学领域最重要的进步之一。然而，传统疫苗在设计和生产成本方面存在一些缺点。基于肽的疫苗是一种有吸引力的替代品，因为它们主要可以通过计算机设计，可以廉价和安全地生产，并且能够诱导针对保护性表位的免疫反应。然而，需要进行适当的肽设计，不仅要产生针对肽的特异性免疫反应，还要在自然感染时识别天然蛋白质。在此，我们提出了一种开发基于肽的疫苗的合理工作流程，包括保证对天然蛋白质进行交叉识别的新步骤。在这方面，我们通过选择无翻译后修饰的线性 B 细胞表位来增加产生有效抗体的可能性，然后分析溶液中的肽与亲本天然蛋白质中肽的 3D 结构相似性。作为概念验证，该工作流程应用于一组七个先前建议的针对阔节裂头绦虫感染的潜在保护性抗原。最后，获得了两个肽，它们具有诱导特异性抗体的能力，能够在不同的体外环境中发挥抗寄生虫活性，并在继发性棘球蚴病的小鼠模型中提供显著的保护作用。
