背景:产志贺毒素的大肠杆菌(STEC)O157:H7和O104:H4菌株是食源性疾病的重要病原体,例如出血性结肠炎和溶血性尿毒症综合征,这是5岁以下儿童以及老年人肾衰竭和死亡的主要原因。
方法:将天然大肠杆菌O157:H7和O104:H4脂多糖(LPS)在碱性条件下部分脱酰,以获得具有三酰化脂质A物种-Ac3-S-LPS控制的致热S-LPS。
结果:用来自大肠杆菌O157:H7和O104:H4的Ac3-S-LPS抗原或其组合(双疫苗)以25至250µg的单剂量对BALB/c小鼠进行腹膜内免疫诱导高滴度的血清O特异性IgG(主要是IgG1),保护动物免受致死剂量的同源STEC菌株的腹膜内攻击(60-100%的存活率),并在体内鼠模型下减少了大肠杆菌O157:H7和O104:H4的肠道定植(单价Ac3-S-LPS为6-8倍,双疫苗为10倍)。
结论:Di疫苗在小鼠中同时诱导针对两种高毒力人类STEC菌株的全身和肠道抗定植免疫。由于致病性大肠杆菌的大量血清型多样性,基于安全的Ac3-S-LPS产生多价STEC疫苗的可能性似乎特别有希望。
BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and O104:H4 strains are important causative agents of food-borne diseases such as hemorrhagic colitis and hemolytic-uremic syndrome, which is the leading cause of kidney failure and death in children under 5 years as well as in the elderly.
METHODS: the native E. coli O157:H7 and O104:H4 lipopolysaccharides (LPS) were partially deacylated under alkaline conditions to obtain apyrogenic S-LPS with domination of tri-acylated lipid A species-Ac3-S-LPS.
RESULTS: intraperitoneal immunization of BALB/c mice with Ac3-S-LPS antigens from E. coli O157:H7 and O104:H4 or combination thereof (di-vaccine) at single doses ranging from 25 to 250 µg induced high titers of serum O-specific IgG (mainly IgG1), protected animals against intraperitoneal challenge with lethal doses of homologous STEC strains (60-100% survival rate) and reduced the E. coli O157:H7 and O104:H4 intestinal colonization under an in vivo murine model (6-8-fold for monovalent Ac3-S-LPS and 10-fold for di-vaccine).
CONCLUSIONS: Di-vaccine induced both systemic and intestinal anti-colonization immunity in mice simultaneously against two highly virulent human STEC strains. The possibility of creating a multivalent STEC vaccine based on safe Ac3-S-LPS seems to be especially promising due to a vast serotype diversity of pathogenic E. coli.