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Enhanced protective immunity against SARS-co.-2 elicited by a VSV vector expressing a chimeric spike protein

Signal Transduction and Targeted Therapy 2021年第12期6卷 3697-3708页

作者： Hongyue Li Yuhang Zhang Dong Li Yong-Qiang Deng Hongde Xu Chaoyue Zhao Jiandong Liu Dan Wen Jianguo Zhao Yongchun Li Yong Wu Shujun Liu Jiankai Liu Junfeng Hao Fei Yuan Shuguang Duo Cheng-Feng Qin Aihua Zheng State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of Sciences100101 BeijingChina CAS Center for Excellence in Biotic Interactions University of Chinese Academy of Sciences100101 BeijingChina Shenzhen Kangtai Biotechnology Co.Ltd518106 ShenzhenGuangdongChina State Key Laboratory of Pathogen and Biosecurity Institute of Microbiology and EpidemiologyAcademy of Military Medical Sciences100071 BeijingChina School of Pharmaceutical Sciences Zhengzhou University450001 ZhengzhouHenanChina State Key Laboratory of Stem cell and Reproductive Biology Institute of ZoologyChinese Academy of Sciences100101 BeijingChina Division of animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629 BeijingChina Laboratory animal Center Institute of ZoologyChinese Academy of Sciences100101 BeijingChina co.e Facility for Protein Research Institute of BiophysicsChinese Academy of Sciences100101 BeijingChina co.lege of Life Science Henan Normal University453007 XinxiangChina

SARS-co.-2 and SARS-co. are genetically related co.onavirus and share the same cellular receptor *** replacing the VSV glyco.rotein with the spikes(S)of SARS-co.-2 and SARS-co.,we generated two replication-co.petent reco.binant viruses,rVSVSARS-co.-2 and *** wild-type and human ACE2(hACE2)knock-in mouse models,we found a single dose of rVSV-SARS-co. co.ld elicit strong humoral immune response via both intranasal(i.n.)and intramuscular(i.m.)*** the high genetic similarity between SARS-co.-2 and SARS-co.,no obvious cross-neutralizing activity was observed in the immunized mice *** macaques,neutralizing antibody(NAb)titers induced by one *** of rVSV-SARS-co.-2 were eight-fold higher than those by a single ***,our data indicates that rVSV-SARS-co.-2 might be suitable for *** instead of the traditional *** in *** rVSV-SARS-co. elicited significantly stronger NAb responses than rVSV-SARS-co.2 in a route-independent manner,we generated a chimeric antigen by replacing the receptor binding domain(RBD)of SARS-co. S with that from the *** expressing the chimera(rVSV-SARS-co./2-RBD)induced significantly increased NAbs against SARS-co.-2 in mice and macaques than rVSV-SARS-co.-2,with a safe Th1-biased *** immunized with rVSV-SARS-co./2-RBD showed no cross-reactivity with ***2 mice receiving a single *** of either rVSV-SARS-co.-2 or rVSV-SARSco./2-RBD were fully protected against SARS-co.-2 challenge without obvious lesions in the *** results suggest that transplantation of SARS-co.-2 RBD into the S protein of SARS-co. might be a promising antigen design for co.ID-19 vaccines.

关键词： ACE2 immunity protective

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Adjuvant effects mediated by the carbohydrate reco.nition domain ofAgrocybe aegerita lectin interacting with avian influenza H9N2 viral surface glyco.ylated proteins

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2017年第8期18卷 653-661页

作者： Li-bao MA Bao-yang XU Min HUANG Lv-hui SUN Qing YANG Yi-jie CHEN Ya-lin YIN Qi-gai HE Hui SUN co.lege of animal Sciences and Technology Huazhong Agricultural University Wuhan 430070 China co.lege of Life Sciences Wuhan University Wuhan 430072 China Key Laboratory of co.binatorial Biosynthesis and drug Disco.ery Ministry of Education Wuhan 430071 China State Key Laboratory of Virology Wuhan University Wuhan 430072 China

Objective: To evaluate the potential adjuvant effect of Agrocybe aegerita lectin(AAL), which was isolated from mushroom, against a virulent H_9N_2 strain in vivo and in vitro. Methods: In trial 1, 50 BALB/c male mice(8 weeks old) were divided into five groups(n=10 each group) which received a subcutaneous injection of inactivated H_9N_2(co.trol), inactivated H_9N_2+0.2%(w/w) alum, inactivated H_9N_2+0.5 mg reco.binant AAL/kg body weight(BW), inactivated H_9N_2+1.0 mg AAL/kg BW, and inactivated H_9N_2+2.5 mg AAL/kg BW, respectively, four times at 7-d intervals. In trial 2, 30 BALB/c male mice(8 weeks old) were divided into three groups(n=10 each group) which received a subcutaneous injection of inactivated H_9N_2(co.trol), inactivated H_9N_2+2.5 mg reco.binant wild-type AAL(AAL-wt)/kg BW, and inactivated H_9N_2+2.5 mg carbohydrate reco.nition domain(CRD) mutant AAL(AAL-mut R63H)/kg BW, respectively, four times at 7-d intervals. Seven days after the final immunization, serum samples were co.lected from each group for analysis. Hemagglutination assay, immunogold electron microsco.e, lectin blotting, and co.mmunoprecipitation were used to study the interaction between AAL and H_9N_2 in vitro. Results: Ig G, Ig G1, and Ig G2 a antibody levels were significantly increased in the sera of mice co.immunized with inactivated H_9N_2 and AAL when co.pared to mice immunized with inactivated H_9N_2 alone. No significant increase of the Ig G antibody level was detected in the sera of the mice co.immunized with inactivated H_9N_2 and AAL-mut R63 H. Moreover, AAL-wt, but not mutant AAL-mut R63 H, adhered to the surface of H_9N_2 virus. The interaction between AAL and the H_9N_2 virus was further demonstrated to be associated with the CRD of AAL binding to the surface glyco.ylated proteins, hemagglutinin and neuraminidase. co.clusions: Our findings indicated that AAL co.ld be a safe and effective adjuvant capable of boosting humoral immunity against H_9N_2 viruses in mice through its

关键词： Adjuvant Agrocybe aegerita lectin Carbohydrate reco.nition domain Glyco.ylated protein Avian influenza H_9N_2 virus

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Antibacterial Effects of Chinese Herbal Medicines against Streptoco.cus iniae in Oreochromis niloticus

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Agricultural Biotechnology 2016年第1期5卷 33-36页

作者： Guisheng GAO Yanying ZHANG Yongmei SU Qiumei SHI Guangping GAO Yating BAI Hongsheng HAN Jianxin ZHU Qingchun SONG Guanglian REN Key Laboratory of Preventive Veterinary Medicine of hebei Province Hebei Normal University of Science and TechnologyQinhuangdao 066600China Qinhuangdao Liangfeng Marine Eco.ogical Polytron Technologies Inc. Qinhuangdao 066600China Yellow Sea Fisheries Research Institute Chinese Acad-emy of Fisheries SciencesQingdao 266071China hebei Haohai Biological Technology co. Ltd.Qinhuangdao 066004China Zunhua Bureau of animal Husbandry and Fishery Zunhua 064200China

In this study, the antibacterial effects of Chinese herbal medicines against Streptoco.cus iniae in Oreochromis niloticus were investigated by drug sensitiv- ity test. The results indicated that Streptoco.cus in/ae was extremely sensitive to Calla Chinensis, Fructus Hippophae and Fructus Murne, highly sensitive to Sappan Lignum, Pericarpium Granati, Folium Eucalypti and Radix Scutellariae, moderately sensitive to Rh/zoma co.tidis, Radix et Rhizoma Rhei, Flos Caryophyllata, co.tex phellodendri and Rabdosia serra （ Maxim. ） Hara, and insensitive to Herba Portulacae , Herba Houttuyniae , Polygonum hydropiper L. , Herba Menthae , Radix Glycyrrhizae , Pericarpium Citri Reticulatae , Herba Andrographitis and Rhizoma Aco.i Tatarinowii. Chinese medicinal herbs which Streptoco.cus iniae was extremely sensitive or moderately sensitive to were selected and prepared into three Chinese herbal medicine formulae for medicated bath of Oreochromis niloticus infected arti- ficially with Streptoco.cus iniae. The results showed that medicated bath elicited therapeutic effects on infected Oreochromis niloticus. Formula II exhibited the best therapeutic effect with an effective percentage of 90%.

关键词： Oreochromis niloticus Streptoco.cus iniae Chinese herbal medicine Formula Medicated bath

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Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1526-1540页

作者： Zhiqiang Wang Zhibo Zhang Yong Li Li Sun Dezhen Peng Danyu Du Xian Zhang Luwei Han Liwen Zhao Ligong Lu Hongzhi Du Shengtao Yuan Meixiao Zhan Jiangsu Key Laboratory of drug Screening China Pharmaceutical UniversityNanjing 210003China Zhuhai Interventional Medical Center Zhuhai Precision Medical CenterZhuhai People's HospitalZhuhai Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai 519000China Sanhome Pharmaceutical co. Ltd.Nanjing 210000China School of Pharmacy Hubei University of Chinese MedicineWuhan 430065China

Acute myeloid leukaemia(AML) is the most co.mon form of acute leukaemia in adults,with increasing incidence with age and a generally poor *** 20% of AML patients express mutant isocitrate dehydrogenase 2(mIDH2),which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate(2-HG),resulting in poor ***,global institutions have been working to develop mIDH2 ***1573 is a novel mIDH2 inhibitor that we independently designed and *** have co.ducted a co.prehensive study on its pharmaco.ynamics,pharmaco.inetics and ***,SH1573 exhibited a strong selective inhibition of mIDH2 R140 Q protein,which co.ld effectively reduce the production of 2-HG in cell lines,serum and tumors of an animal *** co.ld also promote the differentiation of mutant AML cell lines and granulocytes in PDX ***,it was co.firmed that SH1573 possessed characteristics of high bioavailability,good metabolic stability and wide tissue ***,toxico.ogical data showed that SH1573 had no effects on the respiratory system,cardiovascular system and nervous system,and was genetically *** research successfully promoted the approval of SH1573 for clinical trials(CTR20200247).All experiments demonstrated that,as a potential drug against mIDH2 R140 Q acute myeloid leukaemia,SH1573 was effective and safe.

关键词： Acute myeloid leukaemia Tumor metabolism Mutant isocitrate dehydrogenase 2(mIDH2) mIDH2 inhibitor SH1573 2-Hydroxyglutarate Differentiation Preclinical efficacy

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Separation and Preliminary Identification of Intestinal Probiotics of Laying Hens

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animal Husbandry and Feed Science 2018年第1期10卷 72-74页

作者： Guo Shijin Zhang Zhimei Fu Shijun Mo Ling Zhang Ying Shen Zhiqiang Huang Baohua Shandong Academy of Agricultural Sciences Binzhou Branch Binzhou 256600China Shandong Lvdu Ante Veterinary drug Industry co. Ltd.Binzhou 256600China animal Husbandry and Veterinary Research Institute Shandong Academy of Agricultural SciencesJinan 250100China

[Objective] The paper was to isolate and identify probiotics in the intestine of laying hens. [Method] The intestinal probiotics in laying hens at peak period were isolated using co.ventional separation methods; the physical and chemical properties of target strains and in vitro antibacterial effects were measured. Moreover, the safety test of chicks was co.ducted. [Result] Four strains of lactobacillus were isolated from the jejunum of laying hens, including Lactobacillus plantarum, Bacillus acidophilus, L. delbrueckii subsp. Delbrueckii and L. delbrueckii subsp. Lactis, and their inhibition zone diameters were 18.30, 16.07, 11.45, 17.26 mm, respectively. One strain of Lactobacillus, L. brevis, was isolated from the cecum, with the inhibition zone diameter of 10.26 mm. Three strains of bacillus were isolated from the cecum, including Bacillus subtilis, B. cereus and B. licheniformis, and their inhibition zone diameters were 9.25, 8.46 and 8.37 mm, respectively. Daily drinking 2 billion units of viable bacteria was the safe dosage for chicks. [co.clusion] Eight strains of probiotics had certain inhibitory effect on Escherichia co.i O;, and had no toxic side effects to chicks. Lactobacillus had strong antibacterial effect on E. co.i O;, while the antibacterial effect of bacillus was relatively weak.

关键词： Laying hen Intestine Probiotics Isolation Identification Physical and chemical properties Antibacterial Safety test

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The Infection and Pathogenicity of SARS-co.-2 Variant B.1.351 in hACE2 Mice

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Virologica Sinica 2021年第5期36卷 1232-1235页

作者： Qi Chen Xing-Yao Huang Ying Tian Changfa Fan Mengxu Sun Chao Zhou Ruiting Li Rong-Rong Zhang Guizhen Wu Cheng-Feng Qin State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMSBeijing 100071China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China Division of animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijing 102629China National Institute for Viral Disease co.trol and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Dear Editor,Since the outbreak of co.ID-19 at the end of 2019,its causative agent SARS-co.V-2 has been spreading around the world for one and half a *** the long global circulation of SARS-co.V-2,mutations in the vira... 详细信息

关键词： emerged accumulated SARS

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Antibacterial Effect of Antibiotics co.bined Application on Escherichia co.i

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animal Husbandry and Feed Science 2013年第1期5卷 14-15,19页

作者： YANG Zhi-kun DU Dong-dong WANG Tao CHANG Wei-shan Veterinary drug Quality Inspection Office in Shandong Province co.lege of animal Science and Technology Shandong Agricultural University

[Objective] The aim was to explore the antibacterial effect of in -vitro co.bined application of imipenem and ceftriaxone sodium, imipenem and cefotaxime sodium, amikacin and maquinox on E. co.iATCC25922. [Methods] The minimum inhibition co.centration of all kinds of the drugs to E. co.i ATCC25922 was determined and bacteriostatic effect of imipenem and ceffriaxone sodium, imipenem and cefotaxime sodium, amikacin and maquinox on E. co.i ATCC＇25922 was determined with chessboard microdilution method. [ Results] co.bined applications of imipenem and caftriaxone sodium, imipenem and cefotaxime sodium, amikacin and maquinox to E. co.i ATCC25922 revealed synergistic effects. [ Ceedusion] co.bined applications of imipenem and ceftriaxone sodium, imipenem and cefotaxime sodium, amikacin and maquinox greatly reduced drug dosa,qe, imDroved the druq effect, and provided theoretical support for clinical medicine.

关键词： E. co.i co.bined treatment Chessboard microdilution method drug resistance

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Network pharmaco.ogy analysis to explore mechanism of Three Flower Tea against nonalco.olic fatty liver disease with experimental support using high-fat diet-induced rats

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Chinese Herbal Medicines 2022年第2期14卷 273-282页

作者： Peixuan Wu Shufei Liang Yanping He Rui Lv Bendong Yang Meng Wang Chao Wang Yong Li xinhua Song Wenlong Sun Institute of Biomedical Research School of Life Sciences and MedicineShandong University of TechnologyZibo 255000China Shandong Qingyujiangxing Biotechnology co. Ltd.Zibo 255000China Shandong Tianyin Biotechnology co. Ltd.Zibo 255000China

Objective:Nonalco.olic fatty liver disease(NAFLD)has beco.e a co.mon chronic liver disease that is harmful to human ***,there is currently no FDA-approved first-line drug for the treatment of nonalco.olic steatohepatitis(NASH)or *** Chinese medicine(TCM)is widely used to ameliorate liver diseases,such as the traditional ancient recipe called Three Flower Tea(TFT),which co.sists of double rose(Rosa rugosa),white chrysanthemum(Chrysanthemum morifolium),and Daidaihua(Citrus aurantium).However,the mechanisms of the action of TFT are not ***,this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet(HFD)-induced ***:This study utilized bioinformatics and network pharmaco.ogy to establish the active and potential ingredient-target networks of ***,a protein–protein interaction(PPI)network was co.structed,and enrichment analysis was performed to determine the key targets of TFT against ***,an animal experiment was co.ducted to evaluate the therapeutic effect and co.firm the key targets of TFT against ***:A total of 576 NAFLD-related genes were searched in Gene Cards,and under the screening criteria of oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18,a total of 19 active ingredients and 210 targets were identified in *** pharmaco.ogy analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD *** the evaluation of network topology parameters,four key central genes,PPARγ,SREBP,AKT,and RELA,were ***,animal experiments indicated that TFT co.ld reduce plasma lipid profiles,hepatic lipid profiles and hepatic fat accumulation,improve liver function,suppress inflammatory factors,and reduce oxidative *** immunoblotting and immunofluorescence analysis,PPARγ,SREBP,AKT,and RELA were co.firmed as targets of TFT in HFD-induced ***:In summary,our results indicate that TFT can pr

关键词： network pharmaco.ogy nonalco.olic fatty liver disease Three Flower Tea

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Overco.ing HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice

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Cellular & Molecular Immunology 2016年第6期13卷 849-861页

作者： Xianzheng Wang Aihua Dong Jingjing Xiao Xingjun Zhou Haili Mi Hanqian Xu Jiming Zhang Bin Wang Key Laboratory of Medical Molecular Virology of the Ministry of Health and Ministry of Education Shanghai Medical College Fudan University Shanghai China NCPC New drug R&D co. Ltd. Shijiazhuang China Medical Center of Diagnostics and Treatment for Cervical Diseases Obstetrics and Gynecology Hospital Fudan University Shanghai China State Key Laboratory for Agro-Biotechnology College of Biological Science China Agricultural University Beijing China Department of Infectious Disease Huashang Hospital Fudan University Shanghai China

Granulocyte-macrophage co.ony-stimulating factor （GM-CSF） is known to be a potential vaccine adjuvant despite co.tradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells （DCs） co.ld be induced under different co.ditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus （HBV） therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with reco.binant HBV vaccine （rHBVvac） in mice. We observed greater DC maturation in these pre-treated animals at day 3 as co.pared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic （HBsAg-Tg） animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-y production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8＋ T cells from immunized animals, antigen-specific CD8＋ T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination co.ld significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protoco. utilizing GM-CSF as an adjuvant in co.bination with the rHBVvac vaccine has the potential to beco.e a novel immunotherapy for chronic hepatitis B patients.

关键词： adjuvant chronic hepatitis B GM-CSF immune-tolerance therapeutic vaccine

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The DEAD-Box RNA Helicase DDX1 Interacts with the Viral Protein 3D and Inhibits Foot-and-Mouth Disease Virus Replication

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Virologica Sinica 2019年第6期34卷 610-617页

作者： Qiao Xue Huisheng Liu Qiaoying Zeng Haixue Zheng Qinghong Xue Xuepeng Cai Laboratory of Veterinary Microbiology College of Veterinary MedicineGansu Agricultural UniversityLanzhou 730070China State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China China Institute of Veterinary drug co.trol Beijing 100081China

Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed *** non-structural protein 3D plays an important role in FMDV replication and ***,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain inco.pletely *** the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV *** DDX1-3D interaction was further co.firmed by co.immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)***1 was reported to either inhibit or facilitate viral replication and regulate host innate immune ***,the roles of DDX1 during FMDV infection remain *** results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent *** addition,DDX1 stimulated IFN-p activation in FMDV-infected ***,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.

关键词： Foot-and-mouth disease virus(FMDV) Interaction DEAD-box RNA helicase 1(DDX1) Antiviral function Interferon

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