1.Engineered Escherichia coli Nissle 1917 targeted delivery of extracellular PD-L1-mFc fragment for treating inflammatory bowel disease.
Yuhong WANG ; Lin HU ; Lei WANG ; Chonghai ZHANG ; Wenhao SHEN ; Hongli YANG ; Min LI ; Xin ZHANG ; Mengmeng XU ; Muxing ZHANG ; Kai YANG ; Xiaopeng TIAN
Acta Pharmaceutica Sinica B 2025;15(11):6019-6033
Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔpMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.
2.Analysis of epidemiological and pathogenic characteristics of a mumps outbreak in a school in Xining, Qinghai province
Zhifang ZHANG ; Ning XU ; Jing WU ; Chonghai LI ; Xiaotong WANG ; Aili CUI ; Lixia FAN
Chinese Journal of Experimental and Clinical Virology 2020;34(4):401-405
Objective:To investigate the epidemiological and pathogenic characteristics of a mumps outbreak in a primary school in Xining, Qinghai province.Methods:The epidemiological investigation was carried out to analyze the epidemiological distribution of mumps cases in the outbreak. Serum and throat swab samples were collected from 9 suspected mumps cases for laboratory testing. The throat swab samples detected positive for nucleic acid of mumps virus were subjected to virus isolation. Then the SH gene was amplified by RT-PCR for positive virus isolates, and the genotypes of mumps virus were identified and gene characteristics were analyzed.Results:A total of 13 cases were reported in this outbreak. The age of cases was mainly 7-11 years old, and the cases were mainly concentrated at 8 years old (69.23%. 9/13). The male to female ratio is 1.6: 1. None of the 13 cases had a history of mumps vaccination. And there was an obvious in-class clustering in this mumps outbreak. Of the 9 suspected mumps cases, 8 were double positive for mumps specific IgM antibody and viral nucleic acid. Two positive mumps virus isolates were obtained and identified by genotyping as F genotype, and the SH gene sequence of the two mumps virus isolates had 100% homology.Conclusions:This outbreak is caused by genotype F mumps virus. MuV immunization activities were recommended to conduct among unvaccinated students in primary and secondary schools.
3. Genetic characteristics of VP1 region of enterovirus Coxsackievirus A16 in Xining city from 2017 to 2018
Haijie GENG ; Liping REN ; Yongjian FENG ; Huirong ZHANG ; Xiaohong WANG ; Chonghai LI ; Xiaotong WANG ; Lixia FAN
Chinese Journal of Experimental and Clinical Virology 2019;33(5):482-484
Objective:
To investigate the genetic characteristics of VP1 coding region of enterovirus Coxsackievirus A16(CV-A16) and etiological features of hand, foot and mouth disease (HFMD) in 2017 in Xining city.
Methods:
The pharyngeal swab specimens were collected from HFMD patients, and detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). For CV-A16 positive samples, virus isolation was performed. Then RNA was extracted, and then VP1 coding region was amplified by RT-PCR. The phylogenetic tree was constructed by comparing with other genotypes and sub-genotypes strains of EV-A71.
Results:
It was shown that 70 strains of CV-A16 were isolated from 2017 to 2018 in Xining city. In 2017, 10 strains were isolated and divided into two different lineages by phylogenetic analysis, 3 strains of B1a and 7 stains of B1b. In 2018, 60 stains were isolated, which were all belong to B1b.
Conclusions
B1a and B1b of CV-A16 are prevalent in Xining city from 2017 to 2018, in which B1b is the prominent isolates.

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