Chatterjee Rahul, Mahapatra Soumya Ranjan, Dey Jyotirmayee, Raj Takur Kiran, Raina Vishakha, Misra Namrata, Suar Mrutyunjay
School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar, India.
Department of Biotechnology & Bioinformatics, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru, India.
J Mol Recognit. 2023 Apr;36(4):e3007. doi: 10.1002/jmr.3007. Epub 2023 Feb 21.
Staphylococcus aureus has been widely reported to be majorly responsible for causing nosocomial infections worldwide. Due to an increase in antibiotic-resistant strains, the development of an effective vaccine against the bacteria is the most viable alternative. Therefore, in the current work, an effort has been undertaken to develop a novel peptide-based vaccine construct against S aureus that can potentially evoke the B and T cell immune responses. The fibronectin-binding proteins are an attractive target as they play a prominent role in bacterial adherence and host cell invasion and are also well conserved among rapidly mutating pathogens. Therefore, highly immunogenic linear B lymphocytes (LBL), cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) epitopes were identified from the antigenic fibronectin-binding proteins A and B (FnBPA and FnBPB) of S aureus using immunoinformatics approaches. The selected peptides were confirmed to be non-allergenic, non-toxic, and with a high binding affinity to the majority of human leukocyte antigens (HLA) alleles. Consequently, the multi-peptide vaccine construct was developed by fusing the screened epitopes (three LBL, five CTL, and two HTL) together with the suitable adjuvant and linkers. In addition, the tertiary conformation of the peptide construct was modeled and later docked to the Toll-like receptor 2. Subsequently, a molecular dynamics simulation of 100 ns was employed to corroborate the stability of the designed vaccine-receptor complex. Besides exhibiting high immunogenicity and conformational stability, the developed vaccine was observed to possess wide population coverage of 99.51% worldwide. Additional in vivo and in vitro validation studies would certainly corroborate the designed vaccine construct to have improved prophylactic efficacy against S aureus.
金黄色葡萄球菌被广泛报道是全球医院感染的主要致病菌。由于抗生素耐药菌株的增加，开发一种有效的抗该细菌疫苗是最可行的选择。因此，在当前的工作中，人们致力于开发一种新型的基于肽的抗金黄色葡萄球菌疫苗构建体，它有可能引发B细胞和T细胞免疫反应。纤连蛋白结合蛋白是一个有吸引力的靶点，因为它们在细菌黏附和宿主细胞侵袭中起重要作用，并且在快速突变的病原体中也高度保守。因此，使用免疫信息学方法从金黄色葡萄球菌的抗原性纤连蛋白结合蛋白A和B（FnBPA和FnBPB）中鉴定出高免疫原性的线性B淋巴细胞（LBL）、细胞毒性T淋巴细胞（CTL）和辅助性T淋巴细胞（HTL）表位。所选肽被证实无致敏性、无毒性，并且与大多数人类白细胞抗原（HLA）等位基因具有高结合亲和力。因此，通过将筛选出的表位（三个LBL、五个CTL和两个HTL）与合适的佐剂和接头融合，开发了多肽疫苗构建体。此外，对肽构建体的三级构象进行了建模，随后将其对接至Toll样受体2。随后，进行了100纳秒的分子动力学模拟，以证实所设计疫苗 - 受体复合物的稳定性。除了具有高免疫原性和构象稳定性外，所开发的疫苗在全球范围内的人群覆盖率高达99.51%。额外的体内和体外验证研究肯定会证实所设计的疫苗构建体对金黄色葡萄球菌具有更高的预防效果。
