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分子脂多糖双疫苗可预防产志贺毒素的O157:H7和O104:H4流行菌株。

Molecular Lipopolysaccharide Di-Vaccine Protects from Shiga-Toxin Producing Epidemic Strains of O157:H7 and O104:H4.

作者信息

Dyatlov Ivan A, Svetoch Edward A, Mironenko Anna A, Eruslanov Boris V, Firstova Victoria V, Fursova Nadezhda K, Kovalchuk Alexander L, Lvov Vyacheslav L, Aparin Petr G

机构信息

State Research Center for Applied Microbiology and Biotechnology, Rospotrebnadzor, 142279 Obolensk, Moscow Region, Russia.

National Research Center Institute of Immunology Federal Medical-Biology Agency (FMBA of Russia), 115522 Moscow, Russia.

出版信息

Vaccines (Basel). 2022 Nov 1;10(11):1854. doi: 10.3390/vaccines10111854.

Abstract

BACKGROUND

Shiga toxin-producing (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 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-Ac-S-LPS.

RESULTS

intraperitoneal immunization of BALB/c mice with Ac-S-LPS antigens from 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 O157:H7 and O104:H4 intestinal colonization under an in vivo murine model (6-8-fold for monovalent Ac-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 Ac-S-LPS seems to be especially promising due to a vast serotype diversity of pathogenic .

摘要

背景

产志贺毒素大肠杆菌(STEC)O157:H7和O104:H4菌株是食源性疾病(如出血性结肠炎和溶血尿毒综合征)的重要致病原,溶血尿毒综合征是5岁以下儿童以及老年人肾衰竭和死亡的主要原因。

方法

在碱性条件下对天然O157:H7和O104:H4脂多糖(LPS)进行部分脱酰基处理,以获得以三酰化脂质A种类为主的无热原性S-LPS——Ac-S-LPS。

结果

用来自O157:H7和O104:H4的Ac-S-LPS抗原或其组合(二价疫苗)以25至250μg的单剂量对BALB/c小鼠进行腹腔免疫,可诱导产生高滴度的血清O特异性IgG(主要为IgG1),保护动物免受致死剂量同源STEC菌株的腹腔攻击(存活率60 - 100%),并在体内小鼠模型中减少O157:H7和O104:H4在肠道的定植(单价Ac-S-LPS为6 - 8倍,二价疫苗为10倍)。

结论

二价疫苗在小鼠中同时诱导了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血清型种类繁多,基于安全的Ac-S-LPS制备多价STEC疫苗的可能性似乎特别有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1c/9692684/643debbb2e2d/vaccines-10-01854-g001.jpg

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