Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.
Department of Biological Sciences and Biotechnology, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
PLoS One. 2024 Aug 15;19(8):e0306111. doi: 10.1371/journal.pone.0306111. eCollection 2024.
The inability of existing vaccines to cope with the mutation rate has highlighted the need for effective preventative strategies for COVID-19. Through the secretion of immunoglobulin A, mucosal delivery of vaccines can effectively stimulate mucosal immunity for better protection against SARS-CoV-2 infection. In this study, various immunoinformatic tools were used to design a multi-epitope oral vaccine against SARS-CoV-2 based on its receptor-binding domain (RBD) and heptad repeat (HR) domains. T and B lymphocyte epitopes were initially predicted from the RBD and HR domains of SARS-CoV-2, and potential antigenic, immunogenic, non-allergenic, and non-toxic epitopes were identified. Epitopes that are highly conserved and have no significant similarity to human proteome were selected. The epitopes were joined with appropriate linkers, and an adjuvant was added to enhance the vaccine efficacy. The vaccine 3D structure constructs were docked with toll-like receptor 4 (TLR-4) and TLR1-TLR2, and the binding affinity was calculated. The designed multi-epitope vaccine construct (MEVC) consisted of 33 antigenic T and B lymphocyte epitopes. The results of molecular dockings and free binding energies confirmed that the MEVC effectively binds to TLR molecules, and the complexes were stable. The results suggested that the designed MEVC is a potentially safe and effective oral vaccine against SARS-CoV-2. This in silico study presents a novel approach for creating an oral multi-epitope vaccine against the rapidly evolving SARS-CoV-2 variants. These findings offer valuable insights for developing an effective strategy to combat COVID-19. Further preclinical and clinical studies are required to confirm the efficacy of the MEVC vaccine.
现有疫苗无法应对突变率，这凸显了开发针对 COVID-19 的有效预防策略的必要性。通过分泌免疫球蛋白 A，疫苗的黏膜传递可以有效刺激黏膜免疫，更好地预防 SARS-CoV-2 感染。在这项研究中，我们使用了各种免疫信息学工具，根据其受体结合域（RBD）和七肽重复（HR）结构域，设计了一种针对 SARS-CoV-2 的多表位口服疫苗。我们最初从 SARS-CoV-2 的 RBD 和 HR 结构域预测了 T 和 B 淋巴细胞表位，并确定了潜在的抗原性、免疫原性、非变应原性和非毒性表位。选择了高度保守且与人类蛋白质组无显著相似性的表位。将表位与适当的接头连接，并添加佐剂以增强疫苗效力。对接种疫苗的 3D 结构构建体与 Toll 样受体 4（TLR-4）和 TLR1-TLR2 进行对接，并计算结合亲和力。设计的多表位疫苗构建体（MEVC）由 33 个抗原性 T 和 B 淋巴细胞表位组成。分子对接和自由结合能的结果证实，MEVC 能够有效地与 TLR 分子结合，并且复合物稳定。结果表明，设计的 MEVC 是一种针对 SARS-CoV-2 的潜在安全有效的口服疫苗。这项计算机研究为开发针对快速进化的 SARS-CoV-2 变体的口服多表位疫苗提供了一种新方法。这些发现为开发有效的 COVID-19 防治策略提供了有价值的见解。需要进一步的临床前和临床研究来证实 MEVC 疫苗的疗效。
