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

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

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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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Characteristics of animal models for COVID-19

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animal models and Experimental Medicine 2022年第5期5卷 401-409页

作者： Feifei Qi Chuan Qin 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

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19),the most consequential pandemic of this century,threatening human health and public safety.SARS-CoV-2 has been continuously evolving through mutation of its genome and variants of concern have emerged.The World Health Organization R&D Blueprint plan convened a range of expert groups to develop animal models for COVID-19,a core requirement for the prevention and control of SARS-CoV-2 pandemic.The animal model construction techniques developed during the SARS-CoV and MERS-CoV pandemics were rapidly deployed and applied in the establishment of COVID-19 animal models.To date,a large number of animal models for COVID-19,including mice,hamsters,minks and nonhuman primates,have been established.infectious diseases produce unique mani-festations according to the characteristics of the pathogen and modes of infection.Here we classified animal model resources around the infection route of SARS-CoV-2,and summarized the characteristics of the animal models constructed via transnasal,localized,and simulated transmission routes of infection.

关键词： animal model characteristics establishment SARS-CoV-2

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Effectiveness and mechanisms of adiposederived stem cell therapy in animal models of Parkinson’s disease:a systematic review and meta-analysis

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Translational Neurodegeneration 2021年第2期10卷 166-177页

作者： keya Li Xinyue Li Guiying Shi Xuepei Lei Yiying Huang Lin Bai Chuan Qin NHC key laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China

animal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells(ADSCs).Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease(PD).Here,eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention.Quality assessment was conducted using a 10-item risk of bias tool.For the subsequent meta-analysis,study characteristics were extracted and effect sizes were computed.Ten out of 2324 published articles(n=169 animals)were selected for further meta-analysis.After ADSC therapy,the rotation behavior(10 experiments,n=156 animals)and rotarod performance(3 experiments,n=54 animals)were improved(Panimal models of PD.The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects.The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

关键词： Parkinson’s disease Adipose-derived stem cells animal model Stem cell therapy Meta-analysis Neurogenesis Neuroprotection

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Characteristics of gut microbiota in representative mice strains:Implications for biological research

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animal models and Experimental Medicine 2022年第4期5卷 337-349,I0002页

作者： Jianguo Guo Chenchen Song Yunbo Liu Xuying Wu Wei Dong Hua Zhu Zhiguang Xiang Chuan Qin 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

Background:Experimental animals are used to study physiological phenomena,pathological mechanisms,and disease prevention.The gut microbiome is known as a potential confounding factor for inconsistent data from preclinical studies.Although many gut microbiome studies have been conducted in recent decades,few have focused on gut microbiota fluctuation among representative mouse strains.Methods:A range of frequently used mouse strains were selected from 34 isolation packages representing disease-related animal(DRA),immunity defect animal(IDA),or gene-editing animal(GEA)from the BALB/c and C57BL/6J backgrounds together with normal mice,and their microbial genomic DNA were isolated from mouse feces to sequence for the exploration of gut microbiota.Results:Mouse background strain,classification,introduced source,introduced year,and reproduction type significantly affected the gut microbiota structure(p<0.001 for all parameters),with background strain contributing the greatest influence(R^(2)=0.237).In normal groups,distinct gut microbiota types existed in different mouse strains.Sixty-four core operational taxonomic units were obtained from normal mice,and 12 belonged to Lactobacillus.Interestingly,the gut microbiota in C57BL/6J was more stable than that in BALB/c mice.Furthermore,the gut microbiota in the IDA,GEA,and DRA groups significantly differed from that in normal groups(p<0.001 for all).Compared with the normal group,there was a significantly higher Chao 1 and Shannon index(p<0.001 for all)in the IDA,GEA,and DRA groups.Markedly changed classes occurred with Firmicutes and Bacteroidetes.The abundances of Helicobacter,Blautia,Enterobacter,Bacillus,Clostridioides,Paenibacillus,and Clostridiales all significantly decreased in the IDA,GEA,and DRA groups,whereas those of Saccharimonas,Rikenella,and Odoribacter all significantly increased.

关键词： Bacteroidetes BALB/c mice C57BL/6J disease-related animal Firmicutes gene-editing animal gut microbiota i mmunity defect animal strains

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Era of the 4D animal model

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animal models and Experimental Medicine 2023年第2期6卷 178-182页

作者： Lihong Zhang Jindan Guo Jiangning Liu 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

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

关键词： animal model database digitally display human diseases spatiotemporal landscapes

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LasDB: A collective database for laboratory animal strain resources

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animal models and Experimental Medicine 2018年第4期1卷 266-271页

作者： Qi Kong Chuan Qin Institute of laboratory animal Science Chinese Academy of Medical Sciences(CAMS) and Comparative Medicine CenterPeking Union Medical College (PUMC) NHC key laboratory of Human Disease Comparative Medicine Key Laboratory of Human Diseases Animal Model State Administration of Traditional Chinese Medicine Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases beijing Engineering Research Center for Experimental animal models of Human Critical diseases

Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database of all laboratory animal strains,stocks and mutant embryonic stem-cell lines available worldwide, including inbred,outbred, mutant and genetically engineered strains.Methods: MySQL database software was used to construct the LasDB, offering an easy-to-use interface.Results: To date, LasDB has a collection covering data for 21 596 mouse strains,2062 rat strains, 13 monkey strains, 2 hamster strains, 5 dog strains, 5 rabbit strains and more than 50 other laboratory animal strains. LasDB will be continually improved with regular updates of new laboratory animal strains from all over the world.Conclusion: To the best of our knowledge, this is the first database that attempts to systematically integrate all available laboratory animal strain data with the aim of supporting open usage and full resource sharing.

关键词： comparative medicine database laboratory animal resource strain

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Strategies for generating mouse model resources of human disease

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Protein & Cell 2023年第12期14卷 866-870页

作者： Jirong Pan Ling Zhang Zhibing Huang Dalu Zhao He Li Yanan Fu Meng Wang Borui Chen Fuad A.Iraqi Grant Morahan Chuan Qin National Human diseases animal Model Resource Center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesCAMS&PUMCNational Center of Technology Innovation for Animal ModelChangping National Laboratory(CPNL)Beijing 102206China Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityRamat AvivTel Aviv 69978Israel Harry Perkins Institute of Medical Research QEII Medical Centre and Centre for Medical ResearchUniversity of Western AustraliaNedlandsPerthWA 6009Australia

The number of genetically modified mouse models that mimic human disease is growing rapidly,but only a tiny fraction has been commonly used.According to The Knockout Mouse Program(Lloyd,2011),a public resource of mouse embryonic stem cells containing a null mutation in every gene in the mouse genome,8,916 mutant mice lines were phenotyped up to 19 July 2022.Due to the poor correlation between the genomic responses in the mouse models and those responses in human disease,and since humans differ significantly in their genetic vulnerability to common diseases,we still need better mouse models,especially for common and chronic human diseases,including cancer,pulmonary and cardiovascular diseases,obesity and diabetes,behavioral disorders,and neurodegenerative diseases.These new models will be placed into a public repository,The China National Human Disease animal Model Resource Center(NAMR).This project is funded by Ministry of Science and Technology of China and specializes in the creation,introduction,collection,preservation,and supply of animal model resources forhuman diseases.

关键词： diseases cardiovascular generating

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Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer’s disease

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animal models and Experimental Medicine 2021年第3期4卷 233-242页

作者： Zhiqi Song Yajin Qu Yanfeng Xu Ling Zhang Li Zhou Yunlin Han Wenjie Zhao Pin Yu Yu Zhang Xianglei Li Chuan Qin 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

Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.

关键词： 5XFAD mouse model Alzheimer's disease biomarkers microarray miRNA urinary exosome

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The first genetically gene-edited babies: It's “irresponsible and too early”

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animal models and Experimental Medicine 2019年第1期2卷 1-4页

作者： Yuanwu Ma Lianfeng Zhang Chuan Qin key laboratory of Human Disease Comparative Medicine National Health Commission of China (NHC) Institute of Laboratory Animal Science Peking Union Medicine College Chinese Academy of Medical Sciences beijing Engineering Research Center for Experimental animal models of Human Critical diseases Institute of Laboratory Animal Science Peking Union Medicine College Chinese Academy of Medical Sciences Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases

A scientist, Jiankui He of Southern University of Science and Technology of China,recently claimed at the Second International Summit on Human Genome Editing in Hong Kong on 29 November that he has created the world's first genetically altered babies using CRISPR. This announcement sparked controversy and criticism. The newly developed CRISPR/Cas9 technique has been applied to genetic modification of many kinds of animals. However, the technique is still in its infancy and many questions remain to be answered before it can be used for clinical purposes, especially for reproductive purposes.

关键词： animal models animal welfare and ethics Molecular Biology

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