Naorem Romen Singh, Pangabam Bandana Devi, Bora Sudipta Sankar, Fekete Csaba, Teli Anju Barhai
Multidisciplinary Research Unit, Jorhat Medical College and Hospital, Jorhat 785001, India.
Department of Molecular Biology and Microbiology, University of Pecs, Ifusag utja. 6, 7624 Pecs, Hungary.
Pathogens. 2024 Oct 21;13(10):916. doi: 10.3390/pathogens13100916.
Dental caries, a persistent oral health challenge primarily linked to , extends its implications beyond dental decay, affecting over 4 billion individuals globally. Despite its historical association with childhood, dental caries often persists into adulthood with prevalence rates ranging from 60 to 90% in children and 26 to 85% in adults. Currently, there is a dearth of multiepitope vaccines (MEVs) specifically designed to combat . To address this gap, we employed an immunoinformatics approach for MEV design, identifying five promising vaccine candidates (PBP2X, PBP2b, MurG, ATP-F, and AGPAT) based on antigenicity and conservation using several tools including CELLO v.2.5, Vaxign, v2.0, ANTIGENpro, and AllerTop v2.0 tools. Subsequent identification of linear B-cell and T-cell epitopes by SVMTrip and NetCTL/NetMHC II tools, respectively, guided the construction of a MEV comprising 10 Cytotoxic T Lymphocyte (CTL) epitopes, 5 Helper T Lymphocyte (HTL) epitopes, and 5 linear B-cell epitopes, interconnected by suitable linkers. The resultant MEV demonstrated high antigenicity, solubility, and structural stability. In silico immune simulations showcased the MEV's potential to elicit robust humoral and cell-mediated immune responses. Molecular docking studies revealed strong interactions between the MEV construct and Toll-Like Receptors (TLRs) and Major Histocompatibility Complex (MHC) molecules. Remarkably, the MEV-TLR-4 complexes exhibited a low energy score, high binding affinity, and a low dissociation constant. The Molecular Dynamic (MD) simulation analysis suggested that MEV-TLR-4 complexes had the highest stability and minimal conformational changes indicating equilibrium within 40 nanosecond time frames. Comprehensive computational analyses strongly support the potential of the proposed MEV to combat dental caries and associated infections. The study's computational assays yielded promising results, but further validation through in vitro and in vivo experiments is needed to assess its efficacy and safety.
龋齿是一项主要与……相关的持续性口腔健康挑战,其影响范围超出了牙齿龋坏,全球超过40亿人受其影响。尽管龋齿在历史上常与儿童期相关联,但它在成年期也常常持续存在,儿童患病率在60%至90%之间,成人患病率在26%至85%之间。目前,专门设计用于对抗……的多表位疫苗(MEV)十分匮乏。为了填补这一空白,我们采用免疫信息学方法进行MEV设计,使用包括CELLO v.2.5、Vaxign v2.0、ANTIGENpro和AllerTop v2.0工具在内的多种工具,基于抗原性和保守性确定了五种有前景的疫苗候选物(PBP2X、PBP2b、MurG、ATP - F和AGPAT)。随后分别通过SVMTrip和NetCTL/NetMHC II工具鉴定线性B细胞和T细胞表位,指导构建了一种包含10个细胞毒性T淋巴细胞(CTL)表位、5个辅助性T淋巴细胞(HTL)表位和5个线性B细胞表位的MEV,这些表位通过合适的连接子相互连接。所得的MEV表现出高抗原性、溶解性和结构稳定性。计算机模拟免疫显示MEV有引发强大体液免疫和细胞介导免疫反应的潜力。分子对接研究揭示了MEV构建体与Toll样受体(TLR)和主要组织相容性复合体(MHC)分子之间的强相互作用。值得注意的是,MEV - TLR - 4复合物表现出低能量得分、高结合亲和力和低解离常数。分子动力学(MD)模拟分析表明,MEV - TLR - 4复合物具有最高的稳定性和最小的构象变化,表明在40纳秒时间范围内处于平衡状态。全面的计算分析有力地支持了所提出的MEV对抗龋齿及相关感染的潜力。该研究的计算分析产生了有前景的结果,但需要通过体外和体内实验进一步验证以评估其疗效和安全性。
J Biomol Struct Dyn. 2024-8
Int J Biol Macromol. 2024-1
Drug Discov Today. 2024-9
J Oral Microbiol. 2024-6-3
Microorganisms. 2024-1-7
Comput Biol Med. 2023-6