PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of C8901H13609N2431O2611S48 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.
CONCLUSIONS: However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.
METHODS: 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.
RESULTS: With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of C8901H13609N2431O2611S48 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.
CONCLUSIONS: However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.
摘要：
背景：信使RNA（mRNA）疫苗是对抗感染的有力工具。与传统疫苗不同，这种独特类型的疫苗通过独特的宿主细胞介导的病原体基因表达和抗原呈递引发强大而持久的先天和体液免疫应答.
方法：这提供了一种新的方法来对抗痘病毒科感染。从牛痘和痘病毒的基因组中，三个关键基因(E8L，E7R,选择负责病毒附着和毒力的H3L），并用于设计针对牛痘和水痘病毒感染的候选mRNA疫苗。各种生物信息学工具被用来产生(B细胞，CTL,和HTL)表位，选择其中的28个抗原性和免疫原性表位并连接以形成mRNA疫苗构建体。附加组件,包括一个5'帽子，5\'UTR，佐剂,3\'UTR,和聚（A）尾巴，被纳入以增强稳定性和有效性。实施了安全措施，如人体同源性测试和计算机模拟免疫模拟，以避免自身免疫，并模拟人宿主对设计的mRNA疫苗的免疫反应。分别。通过将其与TLR-2、TLR-3、TLR-4和TLR-9受体对接来评估mRNA疫苗的结合亲和力,随后进行分子动力学模拟以预测结合复合物的稳定性。
结果：人口覆盖率为73%，mRNA疫苗看起来很有前途，分子量为198kDa，分子式为C8901H13609N2431O2611S48，据说具有抗原性，无毒和不过敏，使其安全有效地预防水痘和牛痘病毒感染，与其他insilico设计的痘苗和痘病毒疫苗相比。
结论：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。
方法：这提供了一种新的方法来对抗痘病毒科感染。从牛痘和痘病毒的基因组中，三个关键基因(E8L，E7R,选择负责病毒附着和毒力的H3L），并用于设计针对牛痘和水痘病毒感染的候选mRNA疫苗。各种生物信息学工具被用来产生(B细胞，CTL,和HTL)表位，选择其中的28个抗原性和免疫原性表位并连接以形成mRNA疫苗构建体。附加组件,包括一个5'帽子，5\'UTR，佐剂,3\'UTR,和聚（A）尾巴，被纳入以增强稳定性和有效性。实施了安全措施，如人体同源性测试和计算机模拟免疫模拟，以避免自身免疫，并模拟人宿主对设计的mRNA疫苗的免疫反应。分别。通过将其与TLR-2、TLR-3、TLR-4和TLR-9受体对接来评估mRNA疫苗的结合亲和力,随后进行分子动力学模拟以预测结合复合物的稳定性。
结果：人口覆盖率为73%，mRNA疫苗看起来很有前途，分子量为198kDa，分子式为C8901H13609N2431O2611S48，据说具有抗原性，无毒和不过敏，使其安全有效地预防水痘和牛痘病毒感染，与其他insilico设计的痘苗和痘病毒疫苗相比。
结论：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。
