PdPANA: phagemid display as peptide array for neutralizing antibodies, an engineered in silico vaccine candidate against COVID-19.

IF 2.3
Frontiers in systems biology Pub Date : 2024-06-17 eCollection Date: 2024-01-01 DOI:10.3389/fsysb.2024.1309891
Javier Uzcátegui, Khaleel Mullah, Daniel Buvat de Virgini, Andrés Mendoza, Rafael Urdaneta, Alejandra Naranjo
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Abstract

The COVID-19 pandemic has tested the technical, scientific, and industrial resources of all countries worldwide. Faced with the absence of pharmacological strategies against the disease, an effective plan for vaccinating against SARS-CoV-2 has been essential. Due to the lack of production means and necessary infrastructure, only a few nations could adequately confront this pathogen with a production, storage, and distribution scheme in place. This disease has become endemic in many countries, especially in those that are developing, thus necessitating solutions tailored to their reality. In this paper, we propose an in silico method to guide the design towards a thermally stable, universal, efficient, and safe COVID-19 vaccine candidate against SARS-CoV-2 using bioinformatics, immunoinformatics, and molecular modeling approaches for the selection of antigens with higher immunogenic potential, incorporating them into the surface of the M13 phage. Our work focused on using phagemid display as peptide array for neutralizing antibodies (PdPANA). This alternative approach might be useful during the vaccine development process, since it could bring improvements in terms of cost-effectiveness in production, durability, and ease of distribution of the vaccine under less stringent thermal conditions compared to existing methods. Our results suggest that in the heavily glycosylated region of SARS-CoV-2 Spike protein (aa 344-583), from its inter-glycosylated regions, useful antigenic peptides can be obtained to be used in M13 phagemid display system. PdPANA, our proposed method might be useful to overcome the classic shortcoming posed by the phage-display technique (i.e., the time-consuming task of in vitro screening through great sized libraries with non-useful recombinant proteins) and obtain the most ideal recombinant proteins for vaccine design purposes.

PdPANA:用于中和抗体的噬菌体肽阵列,一种针对COVID-19的工程硅疫苗候选物。
新冠肺炎疫情是对世界各国科技和产业资源的严峻考验。面对缺乏针对该疾病的药理学策略,制定有效的SARS-CoV-2疫苗接种计划至关重要。由于缺乏生产手段和必要的基础设施,只有少数国家能够通过适当的生产、储存和分配方案充分应对这种病原体。这种疾病在许多国家,特别是在发展中国家已成为地方病,因此有必要根据这些国家的实际情况采取解决办法。在本文中,我们提出了一种利用生物信息学、免疫信息学和分子建模方法指导设计热稳定、通用、高效、安全的COVID-19候选疫苗,以针对SARS-CoV-2,选择具有较高免疫原性的抗原,并将其整合到M13噬菌体表面。我们的工作重点是利用噬菌体显示作为肽阵列来中和抗体(PdPANA)。这种替代方法在疫苗开发过程中可能有用,因为与现有方法相比,它可以提高生产的成本效益、耐久性和在不那么严格的热条件下分发疫苗的便利性。我们的研究结果表明,在SARS-CoV-2刺突蛋白(aa 344-583)的重度糖基化区,从其糖基化间区可以获得有用的抗原肽,用于M13噬菌体展示系统。PdPANA,我们提出的方法可能有助于克服噬菌体展示技术带来的经典缺点(即通过大量无用的重组蛋白文库进行体外筛选耗时),并获得最理想的重组蛋白用于疫苗设计。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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