Sreerohini Sagi, Balakrishna Konduru, Parida Manmohan
Division of Food Microbiology, Defence Food Research Laboratory, Mysore, India.
APMIS. 2019 Oct;127(10):671-680. doi: 10.1111/apm.12983. Epub 2019 Aug 28.
Regardless of the communal impact of Shiga toxins, till today neither a specific treatment nor licensed vaccine is available. Lactococcus lactis (L. lactis), generally regarded as safe organism, is well known to provide a valuable approach regarding the oral delivery of vaccines. This study was undertaken to evaluate the protective efficacy of Stx2a1 expressed in nisin-inducible L. lactis, against Shiga toxins (Stx1, Stx2) in mouse model. Oral immunization of BALB/c mice with LL-Stx2a1 elicited significant serum antibody titer with elevated fecal and serum IgA, along with minimized intestinal and kidney damage resulting in survival of immunized animals at 84% and 100% when challenged with 10 × LD of Escherichia coli O157 and Shigella dysenteriae toxins, respectively. HeLa cells incubated with immune sera and toxin mixture revealed high neutralizing capacity with 90% cell survivability against both the toxins. Mice immunized passively with both toxins and antibody mixture survived the observation period of 15 days, and the controls administered with sham sera and toxins were succumbed to death within 3 days. Our results revealed protective efficacy and toxin neutralization ability of LL-Stx2a1, proposing it as an oral vaccine candidate against Shiga toxicity mediated by E. coli O157 and S. dysenteriae.
尽管志贺毒素具有公共影响,但直到今天,既没有特异性治疗方法,也没有获得许可的疫苗。乳酸乳球菌通常被视为安全的生物体,众所周知,它为疫苗的口服递送提供了一种有价值的方法。本研究旨在评估在乳酸乳球菌中表达的Stx2a1对小鼠模型中志贺毒素(Stx1、Stx2)的保护效果。用LL-Stx2a1对BALB/c小鼠进行口服免疫,可引发显著的血清抗体滴度,粪便和血清IgA升高,同时肠道和肾脏损伤最小化,当分别用10×LD的大肠杆菌O157和痢疾志贺氏菌毒素攻击时,免疫动物的存活率分别为84%和100%。与免疫血清和毒素混合物一起孵育的HeLa细胞显示出高中和能力,对两种毒素的细胞存活率为90%。用两种毒素和抗体混合物被动免疫的小鼠在15天的观察期内存活,而给予假血清和毒素的对照组在3天内死亡。我们的结果揭示了LL-Stx2a1的保护效果和毒素中和能力,表明它可作为一种针对大肠杆菌O157和痢疾志贺氏菌介导的志贺氏毒性的口服疫苗候选物。