Negahdari Batul, Sarkoohi Parisa, Ghasemi Nezhad Forozan, Shahbazi Behzad, Ahmadi Khadijeh
Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Heliyon. 2024 Jul 16;10(14):e34690. doi: 10.1016/j.heliyon.2024.e34690. eCollection 2024 Jul 30.
has been identified as a major cause of nosocomial infections. Acinetobacter infections are often difficult to treat with multidrug resistant phenotypes. One of the most effective ways to combat infectious diseases is through vaccination. In this study, an attempt was made to select the most protective and potent immunostimulatory epitopes based on the epitope-rich domains of the ZnuD, OmpA and CarO proteins of to design a vaccine that can protect against this infection. After predicting the epitope of B- and T-cells, seven antigenic regions of three proteins CarO, ZnuD and OmpA, were selected. These regions were bound by a GGGS linker. The binding affinity and molecular interactions of the vaccine with the immune receptors TLR2 and TLR4 were studied using molecular docking analysis. This vaccine design was subjected to in silico immune simulations using C-ImmSim. The designed vaccine was highly antigenic, non-allergenic and stable. TLR2 and TLR4 were selected to analyze the ability of the modeled chimeric protein to interact with immune system receptors. The results showed strong interaction between the designed protein vaccine with TLR2 (-18.8 kcal mol-1) and TLR4 (-15.1 kcal mol-1). To verify the stability of the interactions and the structure of the designed protein, molecular dynamics (MD) simulations were performed for 200 ns. Various analyses using MD showed that the protein structure is stable alone and in interaction with TLR2 and TLR4. The ability of the vaccine candidate protein to stimulate the immune system to produce the necessary cytokines and antibodies against was also demonstrated by the ability of the protein designed using the C-ImmSim web server to induce an immune response. Therefore, the designed protein vaccine may be a suitable candidate for in vivo as well as in vitro studies against infections.
已被确定为医院感染的主要原因。不动杆菌感染通常难以用具有多重耐药表型的药物治疗。对抗传染病最有效的方法之一是通过接种疫苗。在本研究中，试图基于鲍曼不动杆菌ZnuD、OmpA和CarO蛋白的富含表位区域选择最具保护性和强效免疫刺激的表位，以设计一种可预防这种感染的疫苗。在预测B细胞和T细胞表位后，选择了CarO、ZnuD和OmpA三种蛋白的七个抗原区域。这些区域通过GGGS接头连接。使用分子对接分析研究了疫苗与免疫受体TLR2和TLR4的结合亲和力和分子相互作用。使用C-ImmSim对该疫苗设计进行了计算机免疫模拟。所设计的疫苗具有高抗原性、无致敏性且稳定。选择TLR2和TLR4来分析模拟嵌合蛋白与免疫系统受体相互作用的能力。结果表明，所设计的蛋白疫苗与TLR2（-18.8 kcal mol-1）和TLR4（-15.1 kcal mol-1）之间存在强烈相互作用。为了验证相互作用的稳定性和所设计蛋白的结构，进行了200 ns的分子动力学（MD）模拟。MD的各种分析表明，该蛋白结构单独以及与TLR2和TLR4相互作用时都是稳定的。使用C-ImmSim网络服务器设计的蛋白诱导免疫反应的能力也证明了候选疫苗蛋白刺激免疫系统产生针对鲍曼不动杆菌的必要细胞因子和抗体的能力。因此，所设计的蛋白疫苗可能是针对鲍曼不动杆菌感染进行体内外研究的合适候选物。
