Escuela Profesional de Genética y Biotecnología, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima, Peru.
Departamento de Ciencias Celulares y Moleculares, Laboratorio de Bioinformática, Biología Molecular y Desarrollos Tecnológicos, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.
Front Immunol. 2022 Aug 30;13:942907. doi: 10.3389/fimmu.2022.942907. eCollection 2022.
is a dangerous bacterium and known biological warfare weapon associated with several diseases, whose lethal toxins can produce necrosis in humans. However, there is no safe and fully effective vaccine against for humans yet. To address this problem, we computationally screened its whole proteome, identifying highly immunogenic proteins, domains, and epitopes. First, we identified that the proteins with the highest epitope density are Collagenase A, Exo-alpha-sialidase, alpha n-acetylglucosaminidase and hyaluronoglucosaminidase, representing potential recombinant vaccine candidates. Second, we further explored the toxins, finding that the non-toxic domain of Perfringolysin O is enriched in CTL and HTL epitopes. This domain could be used as a potential sub-unit vaccine to combat gas gangrene. And third, we designed a multi-epitope protein containing 24 HTL-epitopes and 34 CTL-epitopes from extracellular regions of transmembrane proteins. Also, we analyzed the structural properties of this novel protein using molecular dynamics. Altogether, we are presenting a thorough immunoinformatic exploration of the whole proteome of , as well as promising whole-protein, domain-based and multi-epitope vaccine candidates. These can be evaluated in preclinical trials to assess their immunogenicity and protection against infection.
是一种危险的细菌，也是已知的与多种疾病相关的生物战剂，其致命毒素可导致人类坏死。然而，目前尚无针对人类的安全、完全有效的疫苗。为了解决这个问题，我们通过计算筛选了其整个蛋白质组，鉴定出了高度免疫原性的蛋白质、结构域和表位。首先，我们发现具有最高表位密度的蛋白质是胶原酶 A、外切-α-唾液酸酶、α n-乙酰氨基葡萄糖苷酶和透明质酸酶，它们代表了潜在的重组疫苗候选物。其次，我们进一步探索了毒素，发现无害溶细胞素 O 的非毒性结构域富含 CTL 和 HTL 表位。该结构域可作为一种潜在的亚单位疫苗用于防治气性坏疽。第三，我们设计了一种包含 24 个 HTL 表位和 34 个 CTL 表位的多表位蛋白，这些表位来自跨膜蛋白的细胞外区域。此外，我们还使用分子动力学分析了该新型蛋白质的结构特性。总之，我们对 的整个蛋白质组进行了全面的免疫信息学探索，并提出了有前途的全蛋白、基于结构域和多表位疫苗候选物。这些候选物可以在临床前试验中进行评估，以评估它们针对 感染的免疫原性和保护作用。
