Division of Vaccine Design and Development, Helix Biogen Institute, Ogbomoso, Oyo State, Nigeria.
Laboratory of Molecular Biology, Immunology and Bioinformatics, Department of Microbiology, Adeleke University, Ede, Osun State, Nigeria.
Immun Inflamm Dis. 2024 Aug;12(8):e1360. doi: 10.1002/iid3.1360.
Messenger RNA (mRNA) vaccines emerged as a powerful tool in the fight against infections. Unlike traditional vaccines, this unique type of vaccine elicits robust and persistent innate and humoral immune response with a unique host cell-mediated pathogen gene expression and antigen presentation.
This offers a novel approach to combat poxviridae infections. From the genome of vaccinia and Mpox viruses, three key genes (E8L, E7R, and H3L) responsible for virus attachment and virulence were selected and employed for designing the candidate mRNA vaccine against vaccinia and Mpox viral infection. Various bioinformatics tools were employed to generate (B cell, CTL, and HTL) epitopes, of which 28 antigenic and immunogenic epitopes were selected and are linked to form the mRNA vaccine construct. Additional components, including a 5' cap, 5' UTR, adjuvant, 3' UTR, and poly(A) tail, were incorporated to enhance stability and effectiveness. Safety measures such as testing for human homology and in silico immune simulations were implemented to avoid autoimmunity and to mimics the immune response of human host to the designed mRNA vaccine, respectively. The mRNA vaccine's binding affinity was evaluated by docking it with TLR-2, TLR-3, TLR-4, and TLR-9 receptors which are subsequently followed by molecular dynamics simulations for the highest binding one to predict the stability of the binding complex.
With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of CHNOS and it is said to be antigenic, nontoxic and nonallergic, making it safe and effective in preventing infections with Mpox and vaccinia viruses, in comparison with other insilico-designed vaccine for vaccinia and Mpox viruses.
However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.
信使 RNA（mRNA）疫苗作为一种对抗感染的强大工具而出现。与传统疫苗不同，这种独特类型的疫苗会引起强大而持久的先天和体液免疫反应，并具有独特的宿主细胞介导的病原体基因表达和抗原呈递。
这为对抗痘病毒感染提供了一种新方法。从痘苗病毒和猴痘病毒的基因组中，选择了三个负责病毒附着和毒力的关键基因（E8L、E7R 和 H3L），用于设计针对痘苗和猴痘病毒感染的候选 mRNA 疫苗。各种生物信息学工具被用于生成（B 细胞、CTL 和 HTL）表位，其中选择了 28 个抗原和免疫原性表位，并将其链接形成 mRNA 疫苗构建体。其他成分，包括 5'帽、5'UTR、佐剂、3'UTR 和 poly(A)尾，被合并以增强稳定性和有效性。安全性措施，如测试人类同源性和计算机免疫模拟，分别被实施以避免自身免疫和模拟人类宿主对设计的 mRNA 疫苗的免疫反应。通过将 mRNA 疫苗与 TLR-2、TLR-3、TLR-4 和 TLR-9 受体对接来评估其结合亲和力，随后进行分子动力学模拟以预测结合复合物的稳定性。
mRNA 疫苗具有 73%的人口覆盖率，前景广阔，分子量为 198 kDa，分子式为 CHNOS，据称它具有抗原性、无毒和无过敏性，使其在预防猴痘和痘苗病毒感染方面安全有效，与其他针对痘苗和猴痘病毒的计算机设计疫苗相比。
然而，正在通过体内和体外技术进行进一步验证，以充分评估其潜力。
