Kumar Mishra Saurav, Kumar Neeraj, Or Rashid Md Harun, Sultana Sharifa, Dawoud Turki M, Bourhia Mohammed, Georrge John J
Department of Bioinformatics, University of North Bengal, Darjeeling, West Bengal, India.
Department of Pharmaceutical Chemistry, Bhupal Nobles' College of Pharmacy, Udaipur, Rajasthan, India.
Front Immunol. 2025 May 20;16:1540253. doi: 10.3389/fimmu.2025.1540253. eCollection 2025.
Currently, HIV (human immunodeficiency virus) infection is one of the leading complications in public health and causes acquired immunodeficiency syndrome (AIDS), especially in the African region. No specific vaccine is available to combat this, with multi-strain variability being one of the hurdles. In this investigation, we employed variability in the epitope of the HIV subtype C targets to introduce mutations and construct an epitope-based vaccine. Four targets were examined to predict the B and T cells (major histocompatibility complex class I and II). Among the predicted epitopes, immunodominant epitopes were selected and were mapped with the identified variable amino acid to incorporate mutation. These selected and mutated epitopes were used for the non-mutated and mutated vaccine construction, considering linker for fusion and adjuvant to improve the activity. The vaccine's structure was modeled and examined to validate its structural quality, and a high population coverage was also found. The docking investigation of the non-mutated and mutated vaccine with Toll-like receptor 3 shows remarkable activity followed by strong binding affinity, and the simulation of over 100 ns revealed the constancy of the complex system. The immune response revealed its strong effectiveness by generating multiple immunoglobulins followed by the time step of infection, and further, cloning demonstrated a high expression in based on their favorable Codon Adaptation Index and GC value. The integrated approach in this investigation will help to plan a potent immunodominant vaccine that can work for multiple strains of HIV infection.
目前，人类免疫缺陷病毒（HIV）感染是公共卫生领域主要的并发症之一，会导致获得性免疫缺陷综合征（AIDS），尤其是在非洲地区。目前尚无特效疫苗来对抗这一疾病，多种毒株的变异性是障碍之一。在本研究中，我们利用HIV C亚型靶点表位的变异性引入突变，构建了一种基于表位的疫苗。研究了四个靶点以预测B细胞和T细胞（主要组织相容性复合体I类和II类）。在预测的表位中，选择免疫显性表位，并将其与已鉴定的可变氨基酸进行定位以引入突变。考虑到用于融合的接头和佐剂以提高活性，将这些选择并突变的表位用于未突变和突变的疫苗构建。对疫苗的结构进行建模和检查以验证其结构质量，并且还发现其具有高人群覆盖率。未突变和突变疫苗与Toll样受体3的对接研究显示出显著的活性以及较强的结合亲和力，超过100纳秒的模拟揭示了复合系统的稳定性。免疫反应通过产生多种免疫球蛋白以及感染的时间进程显示出其强大的有效性，此外，克隆显示基于其良好的密码子适应指数和GC值在[具体内容缺失]中有高表达。本研究中的综合方法将有助于设计一种对多种HIV感染毒株有效的强效免疫显性疫苗。
