Luo Fumei, Xu Chuanfei, Zhang Chengwen, Tan Aomo, Lu Dongshui, Luo Ping, Cheng Ping, Zhang Weijun, Bai Lijuan, Yu Cuiyun, Sun Si, Zeng Hao, Zou Quanming
School of Pharmacy, University of South China, Hunan, China.
National Engineering Research Center of Immunological Products, Third Military Medical University, Chongqing, China.
Front Immunol. 2024 Nov 21;15:1490044. doi: 10.3389/fimmu.2024.1490044. eCollection 2024.
() possesses numerous virulence factors, with the increasing prevalence of drug-resistant strains heightening the threat posed by this pathogen. Staphylococcal enterotoxin B (SEB), a highly conserved toxin secreted by , is also recognized as a potential bioweapon with super-antigenic activity. SEB represents a promising target in efforts to combat infections caused by . We developed mRNA-based vaccine and antibody targeting SEB for both prophylactic and therapeutic purposes in varying infection conditions. The mSEB mRNA vaccine (10 μg per mouse) induces more robust and persistent immune responses, including higher antibody titers and specific cellular immune responses, compared to immunization with 30 μg of mSEB protein adjuvanted with aluminum phosphate. Additionally, the anti-SEB mRNA antibody maintains secretion of anti-SEB monoclonal antibody (mAb) with a dosage that is 10 times lower than purified protein administration. The mRNA-based antibody exhibits superior pharmacokinetic profiles compared to its protein counterparts, efficiently neutralizing SEB and clearing from circulation. Both the mRNA vaccine and mRNA antibody demonstrate preventive and therapeutic effects by eliciting specific immune responses and generating high-affinity antibodies in mice. We have laid the groundwork for the development and evaluation of mRNA-based vaccines and antibodies targeting SEB produced by . Our studies demonstrate that these approaches are more effective than traditional protein-based vaccines and antibodies in terms of inducing immune responses, pharmacokinetics, and their prophylactic or therapeutic efficacy against infections.
()具有众多毒力因子,随着耐药菌株的日益流行,这种病原体构成的威胁也在增加。葡萄球菌肠毒素B(SEB)是由()分泌的一种高度保守的毒素,也被认为是一种具有超抗原活性的潜在生物武器。SEB是对抗由()引起的感染的一个有前景的靶点。我们开发了基于mRNA的疫苗和靶向SEB的抗体,用于在不同的感染条件下进行预防和治疗。与用30μg磷酸铝佐剂的mSEB蛋白免疫相比,mSEB mRNA疫苗(每只小鼠10μg)诱导出更强壮和持久的免疫反应,包括更高的抗体滴度和特异性细胞免疫反应。此外,抗SEB mRNA抗体以比纯化蛋白给药低10倍的剂量维持抗SEB单克隆抗体(mAb)的分泌。与蛋白质对应物相比,基于mRNA的抗体表现出优异的药代动力学特征,能有效中和SEB并从循环中清除()。mRNA疫苗和mRNA抗体都通过在小鼠中引发特异性免疫反应和产生高亲和力抗体而显示出预防和治疗效果。我们为开发和评估靶向由()产生的SEB的基于mRNA的疫苗和抗体奠定了基础。我们的研究表明,这些方法在诱导免疫反应、药代动力学及其对()感染的预防或治疗效果方面比传统的基于蛋白质的疫苗和抗体更有效。