Kim Jae-Ouk, Nothaft Harald, Moon Younghye, Jeong Seonghun, Vortherms Anthony R, Song Manki, Szymanski Christine M, White Jessica, Walker Richard
Science Unit, International Vaccine Institute, Seoul 08826, Republic of Korea.
VaxAlta Inc., Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Vaccines (Basel). 2025 May 10;13(5):506. doi: 10.3390/vaccines13050506.
: Rising antibiotic resistance underscores the urgent need for effective vaccines against shigellosis. Our previous research identified the 2a truncated mutant (STM), a gene knock-out strain cultivated in shake-flasks, as a promising broadly protective vaccine candidate. Expanding on this finding, our current study explores the feasibility of transitioning to a fermentor-grown STM as a vaccine candidate for further clinical development. : The STM and STM-Cj, engineered to express the conserved N-glycan antigen, were grown in animal-free media, inactivated with formalin, and evaluated for key antigen retention and immunogenicity in mice. : The fermentor-grown STM exhibited significantly increased production yields and retained key antigens after inactivation. Immunization with the STM, particularly along with the double-mutant labile toxin (dmLT) adjuvant, induced robust immune responses to the conserved proteins IpaB, IpaC, and PSSP-1. Additionally, it provided protection against homologous and heterologous challenges in a mouse pulmonary model. The STM-Cj vaccine elicited antibody responses specific to the N-glycan while maintaining protective immune responses against . These findings underscore the potential of the fermentor-grown STM as a safe and immunogenic vaccine platform for combating shigellosis and possibly other gastrointestinal bacterial infections. : Further process development to optimize growth and key antigen expression as well as expanded testing in additional animal models for the assessment of protection against and are needed to build on these encouraging initial results. Ultimately, clinical trials are essential to evaluate the efficacy and safety of STM-based vaccines in humans.
抗生素耐药性不断上升凸显了研发有效志贺氏菌病疫苗的迫切需求。我们之前的研究确定了2a截短突变体（STM），即一种在摇瓶中培养的基因敲除菌株，是一种有前景的具有广泛保护作用的疫苗候选物。基于这一发现，我们目前的研究探索了将其转变为在发酵罐中培养的STM作为候选疫苗用于进一步临床开发的可行性。：将经工程改造以表达保守N -聚糖抗原的STM和STM - Cj在无动物培养基中培养，用福尔马林灭活，并在小鼠中评估关键抗原保留情况和免疫原性。：在发酵罐中培养的STM产量显著提高，灭活后保留了关键抗原。用STM免疫，特别是与双突变不耐热毒素（dmLT）佐剂联合使用时，可诱导对保守蛋白IpaB、IpaC和PSSP - 1产生强烈的免疫反应。此外，它在小鼠肺部模型中提供了针对同源和异源攻击的保护。STM - Cj疫苗引发了针对N -聚糖的特异性抗体反应，同时维持了针对……的保护性免疫反应。这些发现凸显了在发酵罐中培养的STM作为对抗志贺氏菌病以及可能的其他胃肠道细菌感染的安全且具有免疫原性的疫苗平台的潜力。：需要进一步进行工艺开发以优化生长和关键抗原表达，并在更多动物模型中进行扩展测试，以评估针对……和……的保护作用，从而在此令人鼓舞的初步结果基础上继续推进。最终，临床试验对于评估基于STM的疫苗在人类中的疗效和安全性至关重要。
