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Immunogenicity and protective efficacy of a recombinant protein subunit vaccine and an inactivated vaccine against SARS-CoV-2 variants in non-human primates

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1170-1180页

作者： Qian He Qunying Mao Xiaozhong Peng Zhanlong He shuaiyao lu Jialu Zhang Fan Gao Lianlian Bian Chaoqiang An Wenhai Yu Fengmei Yang Yanan Zhou Yun Yang Yanyan Li Yadi Yuan Xujia Yan Jinghuan Yang Xing Wu Weijin Huang Changgui Li Junzhi Wang Zhenglun Liang Miao Xu Division of Hepatitis and Enterovirus Vaccines Institute of Biological ProductsNational Institutes for Food and Drug ControlNHC Key Laboratory of Research on Quality and Standardization of Biotech ProductsNMPA Key Laboratory for Quality Research and Evaluation of Biological ProductsBeijing 102629People’s Republic of China Institute of Medical Biology Chinese Academy of Medicine Sciences&Peking Union Medical CollegeKunming 650118People’s Republic of China

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the *** investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain(RBD)(PS-RBD)and whole inactivated virus particle vaccine(IV)against the variant strains,in this study,rhesus macaques were immunized with PS-RBD or IV vaccine,followed by a Beta variant(B.1.351)*** neutralizing activity against the Beta variant was reduced compared with that against the prototype,the decreased viral load in both upper and lower respiratory tracts,milder pathological changes,and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque ***,PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha,Beta,Delta,and Omicron variants in our study,though the neutralizing antibody(NAb)titers declined by varying degrees,demonstrating potential protection of PS-RBD against current circulating variants of concern(VOCs).Interestingly,although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant,it still showed reduction for viral load and significantly alleviated pathological *** correlates of vaccine-induced protection(CoP)like antibody-dependent cellular cytotoxicity(ADCC)and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.

关键词： protective vaccine neutral

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The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1614-1624页

作者： Li Jiao Yun Yang Wenhai Yu Yuan Zhao Haiting Long Jiahong Gao Kaiyun Ding Chunxia Ma Jingmei Li Siwen Zhao Haixuan Wang Haiyan Li Mengli Yang Jingwen Xu Junbin Wang Jing Yang Dexuan Kuang Fangyu luo Xingli Qian Longjiang Xu Bin Yin Wei Liu Hongqi Liu shuaiyao lu Xiaozhong Peng National Kunming High-Level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunmingYunnanChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina Department of Anatomy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Neurological manifestations are frequently reported in the COVID-19 *** of SARS-CoV-2 remains to be *** this study,we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of *** rhesus monkey,SARS-CoV-2 invades the CNS primarily via the olfactory ***,viruses rapidly spread to functional areas of the central nervous system,such as hippocampus,thalamus,and medulla *** infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons,microglia,and astrocytes in the ***,SARS-CoV-2 infects neuro-derived SK-N-SH,glial-derived U251,and brain microvascular endothelial cells in *** our knowledge,this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model,which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.

关键词： invasion inflammation system

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A core-shell structured COYID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1920-1929页

作者： Ren Yang Yao Deng Baoying Huang Lei Huang Ang Lin Yuhua Li Wenling Wang Jingjing Liu shuaiyao lu Zhenzhen Zhan Yufei Wang Ruhan A Wen Wang Peihua Niu Li Zhao Shiqiang Li Xiaopin Ma luyao Zhang Yujian Zhang Weiguo Yao Xingjie Liang Jincun Zhao Zhongmin Liu Xiaozhong Peng Hangwen Li Wenjie Tan NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Stemirna Therapeutics ShanghaiChina National Institute for Food and Drug Control BeijingChina National Kunming High-level Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina Shanghai East Hospital Tongji UniversityShanghaiChina CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyChinese Academy of Sciences and National Center for Nanoscience and Technology of ChinaBeijingChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Center for Biosafety Mega-Science Chinese Academy of SciencesWuhanHubeiChina

Although inoculation of COVID-19 vaccines has rolled out globally,there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all ***,we report on the development of a highly efficacious mRNA vaccine,SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex(LPP)*** 23 is easy to produce using a large-scale microfluidics-based *** unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability,and a desirable biodistribution pattern with low liver targeting effect upon intramuscular *** evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123,represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2,but also a panel of variants including D614G and N501Y *** addition,SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 *** together,SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.

关键词： vaccine pattern immunity

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Three doses of prototypic SARS-CoV-2 inactivated vaccine induce cross-protection against its variants of concern

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Signal Transduction and Targeted Therapy 2022年第3期7卷 909-917页

作者： Tianhong Xie shuaiyao lu Zhanlong He Hongqi Liu Junbin Wang Cong Tang Ting Yang Wenhai Yu Hua Li Yun Yang Hao Yang Lei Yue Yanan Zhou Fengmei Yang Zhiwu luo Yanyan Li Hong Xiang Yuan Zhao Jie Wang Haixuan Wang Runxiang Long Dexuan Kuang Wenjie Tan Xiaozhong Peng Qihan Li Zhongping Xie Institute of Medical Biology Chinese Academy of Medicine Sciences&Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases650118 KunmingChina The NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDC102206 BeijingChina

Variants are globally emerging very quickly following pandemic prototypic *** evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants,we vaccinated rhesus monkeys with three doses of protot... 详细信息

关键词： doses globally protection

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Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells

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Cellular & Molecular Immunology 2022年第5期19卷 577-587页

作者： Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min luo Ziqi Zhang Tiangi lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang Guobo Shen Guangwen lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song lunzhi Dai Chong Chen Jia Geng Maling Gou lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong shuaiyao lu Xiaozhong Peng Xiawei Wei Laboratory of Aging Research and Cancer Drug Targeting State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan610041China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina Westvac Biopharm Co. Ltd.No.618Fenghuang RoadShuangliu DistrictChengduSichuanChina Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629BeijingChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host *** to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse *** histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino *** acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S ***,histones enhance cell-cell ***,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse *** findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

关键词： COVID-19 SARS-CoV-2 neutrophil extracellular traps histones sialic acid

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云南三个地区野生猕猴的种群结构分析

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兽类学报 2012年第3期32卷 203-208页

作者：赵远王俊斌和占龙禹文海鲁帅尧中国医学科学院/北京协和医学院医学生物学研究所昆明650118

通过齿式及牙齿磨损情况判断年龄及称量体重的方法,对2004年至2010年间从云南景东县、镇沅县、宁蒗县三个地区捕获的23群共670只野生猕猴进行了种群年龄组成、性别比例及体重差异的调查。结果表明:(1)景东县、镇沅县、宁蒗县三地猕猴种... 详细信息

通过齿式及牙齿磨损情况判断年龄及称量体重的方法,对2004年至2010年间从云南景东县、镇沅县、宁蒗县三个地区捕获的23群共670只野生猕猴进行了种群年龄组成、性别比例及体重差异的调查。结果表明:(1)景东县、镇沅县、宁蒗县三地猕猴种群雄雌性别比分别为1∶1.21、1∶1.55、1∶1.52;(2)三个地区猕猴种群年龄结构稳定,幼年组、青年组和中壮年组的个体数量占整个种群数量的80%以上,处于发展阶段;(3)三个地区猕猴种群体重到了中壮年后均出现雄性明显高于雌性(P<0.01)的性二型现象,同时,发现宁蒗县猕猴种群体重明显高于其他两个地区(P<0.01)。以上三个地区野生猕猴种群均处于较高生育高峰,呈现出发展壮大的趋势。本文为云南省猕猴资源的保护与合理开发利用提供一定的依据,同时也为了解云南省野生猕猴群体结构及生长发育规律,建立人工繁育的不同地域(种、亚种)猕猴种质特性数据库和进一步研究提供相应的基础数据支持。

关键词：猕猴性比年龄结构种群性二型

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Comparison of nonhuman primates identified the suitable model for COVID-19

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1102-1110页

作者： shuaiyao lu Yuan Zhao Wenhai Yu Yun Yang Jiahong Gao Junbin Wang Dexuan Kuang Mengli Yang Jing Yang Chunxia Ma Jingwen Xu Xingli Qian Haiyan Li Siwen Zhao Jingmei Li Haixuan Wang Haiting Long Jingxian Zhou Fangyu luo Kaiyun Ding Daoju Wu Yong Zhang Yinliang Dong Yuqin Liu Yinqiu Zheng Xiaochen Lin Li Jiao Huanying Zheng Qing Dai Qiangming Sun Yunzhang Hu Changwen Ke Hongqi Liu Xiaozhong Peng National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijingChina Medical Key Laboratory for Repository and Application of Pathogenic Microbiology Guangdong Provincial Center for Disease Control and PreventionGuangzhouChina

Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains ***,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(***)and Macaca fascicularis(***)and New World monkey Callithrix jacchus(***).Infected *** and *** showed abnormal chest radiographs,an increased body temperature and a decreased body *** genomes were detected in swab and blood samples from all *** load was detected in the pulmonary tissues of *** and *** but not ***,among the three animal species,*** showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary ***,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified *** as the most suitable for modeling COVID-19.

关键词： acute respiratory COV

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Understanding the local structure and thermophysical behavior of Mg-La liquid alloys via machine learning potential

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 439-449页

作者： Jia Zhao Taixi Feng Guimin lu National Engineering Research Center for Integrated Utilization of Salt Lake Resource East China University of Science and TechnologyShanghai 200237China Joint International Laboratory for Potassium and Lithium Strategic Resources East China University of Science and TechnologyShanghai 200237China

The local structure and thermophysical behavior of Mg-La liquid alloys were in-depth understood using deep potential molecular dynamic(DPMD) simulation driven via machine learning to promote the development of Mg-La alloys. The robustness of the trained deep potential(DP) model was thoroughly evaluated through several aspects, including root-mean-square errors(RMSEs), energy and force data, and structural information comparison results;the results indicate the carefully trained DP model is reliable. The component and temperature dependence of the local structure in the Mg-La liquid alloy was analyzed. The effect of Mg content in the system on the first coordination shell of the atomic pairs is the same as that of temperature. The pre-peak demonstrated in the structure factor indicates the presence of a medium-range ordered structure in the Mg-La liquid alloy, which is particularly pronounced in the 80at% Mg system and disappears at elevated temperatures. The density, self-diffusion coefficient, and shear viscosity for the Mg-La liquid alloy were predicted via DPMD simulation, the evolution patterns with Mg content and temperature were subsequently discussed, and a database was established accordingly. Finally, the mixing enthalpy and elemental activity of the Mg-La liquid alloy at 1200 K were reliably evaluated,which provides new guidance for related studies.

关键词： magnesium-lanthanum liquid alloys local structure macroscopic properties thermodynamic behavior deep potential mo-lecular dynamic simulation

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Distinct profiles of Gastrointestinal Microbiota and Metabolites in Rhesus Monkeys Infected with SARS-CoV-2 or Variants

Distinct profiles of Gastrointestinal Microbiota and Metabol...

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第十六届中国实验动物科学年会

作者： Hongyu Chen Junbin Wang Kaiyun Ding Jingwen Xu Yun Yang Cong Tang Yanan Zhou Wenhai Yu Haixuan Wang Qing Huang Bai Li Dexuan Kuang Daoju Wu Zhiwu luo Jiahong Gao Yuan Zhao Jiansheng Liu Xiaozhong Peng shuaiyao lu Hongqi Liu Institute of Medical biology Chinese Academy of Medical Sciences and Peking Union Medical School (IMBCAMS&PUMC) Institute of Basic Medical Sciences IMBCAMS&PUMC Institute of Laboratory Animals Science IMBCAMS&PUMC

Background Accumulating evidences demonstrate that gastrointestinal(GI)infection is involved in pathogenesis of *** of GI microbiota is documented in feces of COVID-19 patients and animal models of SARS-CoV-2 *** evolution of SARS-CoV-2 leads to appearance of distinct viral ***,profiles of GI microbiota and their contribution to infections of SARS-CoV-2 and variants remain to be *** Rhesus monkeys were infected with SARS-CoV-2 or its variants of concern(VOCs),followed by an integrative analysis of histopathology,microbiome and inflammatory responses in fragments of GI *** Five tested strains of SARS-CoV-2 formed two distinct *** viral cluster of Alpha,Beta and Delta(ABD) cause more severe infection and histopathology in both respiratory and gastrointestinal tissues than the cluster of Proto and Omicron(PO).Distinct profile of GI microbiome was observed between two ***,high abundance of potentially pathogenic pathogens,specially Spirocheta,was sequenced in small and large intestines of ABD viral strain infected *** analysis showed that ABD viral strains were positively correlated with infection and immunity-associated metabolites or pathways whereas PO viral strains had negative ***,tryptophanase was upregulated in ABD viral infection,and fatty acid biosynthesis was negatively correlated with PO viral *** analysis of fragments in GI tract showed that ABD viral strains had negative correlations with anti-viral and inhibiting viral binding pathways,including RIG-like receptor signaling pathway that was positively correlated with PO viral ***-and immune-related genes showed lower expressions in ABD virus-infected animals compared with those in PO virus-infected *** contrast,the top five upregulated genes,associated with cancer,inflammation and tight junction,had higher expressions in in ABD virus-infect

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骨髓间充质干细胞移植治疗帕金森病的研究进展

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医药导报 2018年第10期37卷 1227-1233页

作者：李统帅王晚璞杜廷福鲁帅尧陈天星马开利昆明理工大学附属医院、云南省第一人民医院病理科昆明650032 中国医学科学院医学生物学研究所中国医学科学院医学灵长类动物研究中心和神经科学中心云南省重大传染病疫苗研发重点实验室昆明650118

帕金森病是一种中枢神经系统退行性疾病,尽管目前对于帕金森病的研究发展迅速,但是传统的药物治疗只能相应缓解症状,不能阻止疾病的进展,而手术治疗相对危险,且副作用大。骨髓间充质干细胞移植治疗帕金森病目前已成为这一领域的研究主... 详细信息

帕金森病是一种中枢神经系统退行性疾病,尽管目前对于帕金森病的研究发展迅速,但是传统的药物治疗只能相应缓解症状,不能阻止疾病的进展,而手术治疗相对危险,且副作用大。骨髓间充质干细胞移植治疗帕金森病目前已成为这一领域的研究主题之一,由于骨髓间充质干细胞不仅具备多向分化潜能和自我更新能力,还可以作为基因载体治疗帕金森病,是现代神经生物学研究的热点之一,具有广阔的应用前景。该文就骨髓间充质干细胞移植治疗帕金森病的研究进展作一综述。

关键词：帕金森病骨髓间充质干细胞细胞分化移植基因治疗

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