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Sequentially immune-induced antibodies could cross-neutralize SARS-CoV-2 variants

Animal Models and Experimental Medicine 2022年第1期5卷 89-93页

作者： Qi Lv Shasha Zhou Feifei Qi Yaqing Zhang Fengdi Li Mingya Liu Linlin Bao Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina National Center of Technology Innovation for Animal Model BeijingChina

Background:The Omicron(B.1.1.529)SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike protein.Since the vaccine-induced neutralizing antibody targets are the spike protein,this may lead to the possibility of vaccine-induced hu-moral immunity escape.Methods:We measured the neutralizing activity in vitro for Omicron and compared this with wild type(WH-09)and Delta variants in human and monkey sera from different types of immunity.The monkey sera samples were collected at 1 and 3 months post three-dose inactivated(PiCoVacc)and recombinant protein(ZF2001)vaccination.Human sera were collected from 1 month post three-dose inactivated vaccination.Results:In inactivated vaccine sera,at 1/3 months post three-dose,geometric mean titers(GMTs)of neutralization antibody(NAb)against the Omicron variant were 4.9/5.2-fold lower than those of the wild type.In recombinant protein vaccine sera,GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild type.In human sera,at 1 month post three-dose inactivated vaccination,GMTs of NAb against Omicron were 3.1-fold lower than those of the wild type.Conclusion:This study demonstrated that despite a reduction in neutralization titers,cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination.

关键词： cross-neutralize Omicron SARS-CoV-2 sequentially immune

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Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro

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Animal Models and Experimental Medicine 2023年第1期6卷 51-56页

作者： Yaqing Zhang Qi Lv Feifei Qi Fengdi Li Ran Deng Xujian Liang Mingya Liu Yiwei Yan Linlin Bao Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina National Center of Technology Innovation for Animal Model BeijingChina

Background:New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and BA.5.Their pathogenicity has changed from that of wild-type(WH-09)and Omicron variants have over time become globally dominant.The spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants,which is likely to cause immune es-cape and the reduction of the protective effect of the vaccine.Our study addresses the above issues and provides a basis for formulating relevant prevention and control strategies.Methods:We collected cellular supernatant and cell lysates and measured the viral titers,viral RNA loads,and E subgenomic RNA(E sgRNA)loads in different Omicron subvariants grown in Vero E6 cells,using WH-09 and Delta variants as a reference.Additionally,we evaluated the in vitro neutralizing activity of different Omicron sub-variants and compared it to the WH-09 and Delta variants using macaque sera with different types of immunity.Results:As the SARS-CoV-2 evolved into Omicron BA.1,the replication ability in vitro began to decrease.Then with the emergence of new subvariants,the replication ability gradually recovered and became stable in the BA.4 and BA.5 subvariants.In WH-09-inactivated vaccine sera,geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.7~15.4-fold compared to those against WH-09.In Delta-inactivated vaccine sera,geometric mean titers of neutrali-zation antibodies against Omicron subvariants declined by 3.1~7.4-fold compared to those against Delta.Conclusion:According to the findings of this research,the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants,and was lower in BA.1 than in other Omicron subvariants.After two doses of inactivated(WH-09 or Delta)vaccine,cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers.

关键词： cross-neutralize Omicron replication SARS-CoV-2

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Sensitivity of SARS-CoV-2 to different temperatures

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Animal Models and Experimental Medicine 2020年第4期3卷 316-318页

作者： Qi Lv Mingya Liu Feifei Qi Shuran Gong Shasha Zhou Shisheng Zhan Linlin Bao Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

This study was designed to investigate the sensitivity of SARS-CoV-2 to different temperatures,to provide basic data and a scientific basis for the control of COVID-19 epidemic.The virus was dispersed in 1 mL basal DMEM medium at a final concentration of 103.2 TCID 50/mL and then incubated at 4,22,30,35,37,38,39 and 40°C for up to 5 days.The infectivity of residual virus was titrated using the Vero E6 cell line.The results showed that the virus remained viable for 5 days at 4°C,and for 1 day only at 22 and 30°C.We found that the infectivity of the virus was completely lost after less than 12 hours at 37,38 and 39°C,while at 40°C,the inactivation time of the virus was rapidly reduced to 6 hours.We show that SARS-CoV-2 is sensitive to heat,is more stable at lower temperatures than higher temperature,remains viable for longer at lower temperatures,and loses viability rapidly at higher temperatures.

关键词： SARS-CoV-2 sensitivity temperature viability

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A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9

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Chinese Medical Journal 2022年第7期135卷 799-805页

作者： Jingxin Li Li Zhang Linlin Bao Yuxiao Wang Lin Qiu Jialei Hu Rong Tang Huiyan Yu Jun Shan Yan Li Chuan Qin Fengcai Zhu Department for Vaccine Clinical Evaluation NHC Key Laboratory of Enteric Pathogenic MicrobiologyJlangsu Provincial Center for Diseases Control and PreventionNanjingJiangsu 210009China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences(CAMS)&Comparative Medicine CenterPeking Union Medical Collage(PUMC)Key Laboratory of Human Disease Comparative MedicineMinistry of HealthBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesBeijing 100101China Department of Public Health Southeast UniversityNanjingJiangsu 210009China Shanghai Institute for Biological Sciences Chinese Academy of SciencesShanghai 200031China

Background:The new emerging avian influenza A H7N9 virus,causing severe human infection with a mortality rate of around 41%.This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin(HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province,China.The human monoclonal antibodies(mAbs)were generated by amplification and cloning of these HA-specific B cells.First,all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay.Then,those mAbs,exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting(HAI)and microneutralizationin vitro assays.Finally,the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes,including H1N1 and H3N2.The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50(TCID_(50))of H7N9 virus(influenza A/Nanjing/1/2013)invitro,with neutralizing activity as low as 78 ng/mL.In addition,the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

关键词： Avian influenza H7N9 Monoclonal antibody Neutralizing activity

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Seismic behavior of breakwaters on complex ground by numerical tests:Liquefaction and post liquefaction ground settlements

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Earthquake Engineering and Engineering Vibration 2018年第2期17卷 325-342页

作者： Gu linlin Zhang Feng bao Xiaohua Shi Zhenming Ye Guanlin Ling Xianzhang Department of Civil Engineering Qingdao University of Technology Department of Civil Engineering Nagoya Institute of Technology Department of Civil Engineering Shenzhen University Department of Geotechnical Engineering Tongji University Department of Civil Engineering Shanghai Jiao Tong University

A large number of breakwaters have been constructed along coasts to protect humans and infrastructures from tsunamis.There is a risk that foundation soils of these structures may liquefy,or partially liquefy during the earthquake preceding a tsunami,which would greatly reduce the structures’capacity to resist the tsunami.It is necessary to consider not only the soil’s liquefaction behavior due to earthquake motions but also its post-liquefaction behavior because this behavior will affect the breakwater’s capacity to resist an incoming tsunami.In this study,numerical tests based on a sophisticated constitutive model and a soil-water coupled finite element method are used to predict the mechanical behavior of breakwaters and the surrounding soils.Two real breakwaters subjected to two different seismic excitations are examined through numerical simulation.The simulation results show that,earthquakes affect not only the immediate behavior of breakwaters and the surrounding soils but also their long-term settlements due to post-earthquake consolidation.A soil profile with thick clayey layers beneath liquefied soil is more vulnerable to tsunami than a soil profile with only sandy layers.Therefore,quantitatively evaluating the seismic behavior of breakwaters and surrounding soils is important for the design of breakwater structures to resist tsunamis.

关键词： breakwater settlement earthquake numerical test liquefaction

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Therapeutic efficacy of Pudilan Xiaoyan Oral Liquid(PDL)for COVID-19 in vitro and in vivo

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1875-1877页

作者： Wei Deng Yanfeng Xu Qi Kong Jing Xue Pin Yu Jiangning Liu Qi Lv Fengdi Li Qiang Wei Linlin Bao NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed cases.Until now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 infection.Existing medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection.

关键词： vivo fir COV

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硫酸镁联合硝苯地平治疗重度子痫前期效果与不良反应分析

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实用妇科内分泌电子杂志 2022年第35期9卷 10-12页

作者：鲍琳琳睢宁县人民医院妇产科江苏徐州221200

目的探讨硫酸镁联合硝苯地平治疗重度子痫前期效果与不良反应。方法选取重度子痫前期患者50例,以随机数字表法分为对照组与研究组,对照组25例单用硫酸镁,研究组25例联合硝苯地平,对比两组的效果及不良反应。结果研究组临床总有效率高... 详细信息

目的探讨硫酸镁联合硝苯地平治疗重度子痫前期效果与不良反应。方法选取重度子痫前期患者50例,以随机数字表法分为对照组与研究组,对照组25例单用硫酸镁,研究组25例联合硝苯地平,对比两组的效果及不良反应。结果研究组临床总有效率高于对照组;与治疗前比,治疗后两组舒张压、收缩压、24 h尿蛋白、心率、血清肌酐、尿素氮水平均降低,且研究组更低;研究组各项不良妊娠结局发生率均低于对照组,差异具有统计学意义(P<0.05)。结论重度子痫前期在硫酸镁给药基础上给予硝苯地平联用,可提升总有效率,降低血压水平,维持24 h尿蛋白、心率稳定,改善肾功能,改善不良妊娠结局,且具较高的安全性。

关键词：重度子痫前期硫酸镁硝苯地平不良反应

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Population genetic structure in wild and aquaculture populations of Hemibarbus maculates inferred from microsatellites markers

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Aquaculture and Fisheries 2017年第2期2卷 88-93页

作者： linlin Li Hungdu Lin Wenqiao Tang Dong Liu baolong bao Jinquan Yang Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources Ministry of EducationShanghai Ocean UniversityShanghai 201306China The Affiliated School of National Tainan First Senior High School Tainan 701TaiwanChina

The objective of this study was to investigate 4 aquaculture populations Shanghai(SH),Hangzhou(HZ),Kaihua(KH)and Xianju(XJ)and one wild population Yingshan(YS)of spotted barbell(Hemibarbus maculates)to assess their genetic diversity level and investigate the genetic structure of the populations.The dendrogram and STRUCTURE revealed that the populations XJ,KH,and HZ jointly formed one cluster,to which the populations SH and YS were sequentially adhered.The genetic diversity of the cultured populations maintained better,possible due to favourable hatchery conditions that decreased the effect of environmental selection present in wild populations.The results of the present study will contribute to the management of spotted barbell genetic resources,but also demonstrates how the genetic diversity of freshwater species is vulnerable to human activity.

关键词： Population structure jointly

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Escaping alveolar macrophage endosomal retention explains massive expansion of SARS-CoV-2 delta variant

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Signal Transduction and Targeted Therapy 2022年第1期7卷 28-30页

作者： Zhenfeng Wang Yabo Zhou Linlin Bao Dan Li Jiadi Lv Dianheng Wang Shunshun Li Wei-Min Tong Jiangning Liu Chuan Qin Bo Huang Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College100005 BeijingChina NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Department of Pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&Technology430030 WuhanChina

Dear Editor,Genetic variant Delta(B.1.617.2)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which possesses a remarkable ability to transmit and spread,is currently becoming predominant worldwide.Despite its great harm to human beings,how the Delta variant with T478K,P681R and L452R mutations achieves its ultrafast spread remains elusive.Entry of SARS-CoV-2 into host cells is mediated by a rapid enzymatic hydrolysis.

关键词： retention massive delta

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Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71

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Science China(Life Sciences) 2022年第12期65卷 2517-2526页

作者： Zhe Chen Linlin Bao Bin Zhu Hua Fu Shuangli Zhu Tianjiao Ji Ying Xue Chuan Liu Xurong Wang Fengdi Li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo Xu Chuan Qin Hongrong Liu Qi Jin MOH Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China School of Computer Science and Engineering Hunan University of Science and TechnologyXiangtan 411201China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China Ministry of Education Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua UniversityBeijing 100084China Key Laboratory for Matter Microstructure and Function of Hunan Province Key Laboratory of Low-dimensional Quantum Structures and Quantum ControlSchool of Physics and ElectronicsHunan Normal UniversityChangsha 410081China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310058China

Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to death.Currently,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are available.Here,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in cells.The cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of VP1.In a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic treatment.In particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment.

关键词： enterovirus A71 antibody mouse models cryo-electron microscopy

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