Chandpa Hitesh Harsukhbhai, Naskar Shovan, Meena Jairam
ImmunoEngineering and Therapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.
Immunology. 2025 Jun;175(2):180-199. doi: 10.1111/imm.13920. Epub 2025 Mar 8.
Streptococcus pneumoniae is a gram-positive bacterium responsible for various diseases like pneumonia, acute otitis media, sinusitis, meningitis and bacteraemia. These diseases cause a significant amount of morbidity and mortality. Although polysaccharide vaccines are available, the protection provided by these vaccines is serotype-dependent and not enough in sensitive populations like children and older people. Designing a subunit vaccine by using proteins that are responsible for the pathogenesis of diseases can provide better protection against bacterial infections. In this study, we present the design of a novel multi-epitope vaccine against Streptococcus pneumoniae using an immunoinformatic approach. More than 1170 epitopes were identified against B cells, cytotoxic T lymphocytes and helper T lymphocytes from more than 60 pneumococcal proteins. Epitopes were further screened, and potential epitopes were selected for vaccine development. Seven different vaccine combinations that harbour the 15 dominant B-cell, cytotoxic T cell and helper T cell epitopes were evaluated with linker and β-defensin adjuvant to finalise the best vaccine construct. Bioinformatics tools were used to analyse the construct's physicochemical properties, secondary and tertiary structures, allergenicity, antigenicity and immunogenicity. Docking studies with the TLR-4 receptor and molecular dynamics simulations indicated strong binding affinity and stability. In silico immune response simulations predicted robust IgG immune response generation and observed more than 200 000 IgG + IgG counts per mL. Similarly, cell-mediated immunity was also enhanced by the designed vaccine construct. The construct was codon-optimised and cloned in silico for expression in Escherichia coli. These findings suggest that the construct is a promising candidate for further experimental validation.
肺炎链球菌是一种革兰氏阳性细菌，可引发多种疾病，如肺炎、急性中耳炎、鼻窦炎、脑膜炎和菌血症。这些疾病导致大量发病和死亡。尽管有多糖疫苗，但这些疫苗提供的保护是血清型依赖性的，在儿童和老年人等易感人群中作用不足。利用导致疾病发病的蛋白质设计亚单位疫苗可以更好地预防细菌感染。在本研究中，我们采用免疫信息学方法展示了一种新型抗肺炎链球菌多表位疫苗的设计。针对60多种肺炎球菌蛋白，鉴定出了超过1170个针对B细胞、细胞毒性T淋巴细胞和辅助性T淋巴细胞的表位。对表位进行进一步筛选，并选择潜在表位用于疫苗开发。对包含15个主要B细胞、细胞毒性T细胞和辅助性T细胞表位的7种不同疫苗组合，使用接头和β-防御素佐剂进行评估，以确定最佳疫苗构建体。利用生物信息学工具分析构建体的物理化学性质、二级和三级结构、致敏性、抗原性和免疫原性。与TLR-4受体的对接研究和分子动力学模拟表明具有很强的结合亲和力和稳定性。计算机模拟免疫反应预测可产生强大的IgG免疫反应，每毫升观察到超过200000个IgG + IgG计数。同样，设计的疫苗构建体也增强了细胞介导的免疫。对构建体进行密码子优化，并在计算机上克隆以在大肠杆菌中表达。这些发现表明该构建体是进一步实验验证的有前景的候选物。
