Masum Md Habib Ullah, Mahdeen Ahmad Abdullah, Barua Abanti
Department of Genomics and Bioinformatics, Faculty of Biotechnology and Genetic Engineering, Chattogram Veterinary and Animal Sciences University, Khulshi, Chattogram, Bangladesh.
Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh.
Bioinform Biol Insights. 2025 Apr 3;19:11779322251324859. doi: 10.1177/11779322251324859. eCollection 2025.
With the ability to cause massive epidemics that have consequences on millions of individuals globally, the Chikungunya virus (CHIKV) emerges as a severe menace. Developing an effective vaccine is urgent as no effective therapeutics are available for such viral infections. Therefore, we designed a novel mRNA vaccine against CHIKV with a combination of highly antigenic and potential MHC-I, MHC-II, and B-cell epitopes from the structural polyprotein. The vaccine demonstrated well-characterized physicochemical properties, indicating its solubility and potential functional stability within the body (GRAVY score of -0.639). Structural analyses of the vaccine revealed a well-stabilized secondary and tertiary structure (Ramachandran score of 82.8% and a Z-score of -4.17). Docking studies of the vaccine with TLR-2 (-1027.7 KJ/mol) and TLR-4 (-1212.4 KJ/mol) exhibited significant affinity with detailed hydrogen bond interactions. Molecular dynamics simulations highlighted distinct conformational dynamics among the vaccine, "vaccine-TLR-2" and "vaccine-TLR-4" complexes. The vaccine's ability to elicit both innate and adaptive immune responses, including the presence of memory B-cells and T-cells, persistent B-cell immunity for a year, and the activation of TH cells leading to the release of IFN-γ and IL-2, has significant implications for its potential effectiveness. The CHIKV vaccine developed in this study shows promise as a potential candidate for future vaccine production against CHIKV, suggesting its suitability for further clinical advancement, including in vitro and in vivo experiments.
基孔肯雅病毒（CHIKV）能够引发大规模疫情，对全球数百万人造成影响，因此成为一种严重威胁。由于目前尚无针对此类病毒感染的有效治疗方法，开发一种有效的疫苗迫在眉睫。因此，我们设计了一种新型的针对CHIKV的mRNA疫苗，该疫苗结合了来自结构多聚蛋白的高抗原性以及潜在的MHC-I、MHC-II和B细胞表位。该疫苗表现出良好的理化性质，表明其在体内具有溶解性和潜在的功能稳定性（亲水性氨基酸平均疏水性GRAVY值为-0.639）。疫苗的结构分析显示其二级和三级结构稳定（拉氏图得分82.8%，Z值为-4.17）。疫苗与TLR-2（-1027.7 KJ/mol）和TLR-4（-1212.4 KJ/mol）的对接研究显示出显著的亲和力，并伴有详细的氢键相互作用。分子动力学模拟突出了疫苗、“疫苗-TLR-2”和“疫苗-TLR-4”复合物之间不同的构象动力学。该疫苗引发先天和适应性免疫反应的能力，包括记忆B细胞和T细胞的存在、持续一年的B细胞免疫以及导致IFN-γ和IL-2释放的TH细胞激活，对其潜在有效性具有重要意义。本研究开发的CHIKV疫苗有望成为未来生产针对CHIKV疫苗的潜在候选者，表明其适合进一步的临床推进，包括体外和体内实验。
