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Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1768-1776页

作者： Hang Chi Suo-Qun Zhao Ru-Yi Chen Xing-Xing Suo Rong-Rong Zhang Wen-Hui Yang Dong-Sheng Zhou Min Fang Bo Ying Yong-Qiang Deng cheng-feng qin State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMS100071BeijingChina College of Life Sciences Inner Mongolia Agricultural UniversityHohhot010018Inner MongoliaChina School of Life Sciences Henan UniversityKaifeng475004HenanChina Suzhou Abogen Biosciences Co. LtdSuzhou215123JiangsuChina Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical Sciences100071BeijingChina

The Orthopoxvirus genus,especially variola virus(VARV),monkeypox virus(MPXV),remains a significant public health threat *** development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing ***-encoded antibodies have emerged as a powerful and universal platform for rapid antibody ***,by using the established lipid nanoparticle(LNP)-encapsulated mRNA platform,we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against *** vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing *** importantly,mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus(VACV)lethal challenge mouse model,and a unique mRNA antibody cocktail,Mix2a,exhibited superior in vivo protection by targeting both intracellular mature virus(IMV)-form and extracellular enveloped virus(EEV)-form *** summary,our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform,highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as otheremerging viruses.

关键词： proof universal neutral

Seasonal influenza vaccination may mitigate the potential impact of an H5N1 pandemic

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Chinese Medical Journal 2008年第15期121卷 1481-1483页

作者： qin cheng-feng qin E-de State Key Laboratory of Pathogen and Biosecurity Institute of Microbiology and Epidemiology Academy of Military Medical Sciences Beijing 100071 China

Seasonal influenza is a highly contagious, acute respiratory illness that affects people of all ages. The major pathogens, influenza A viruses, are classified into serologically defined antigenic subtypes of the hemagglutinin （HA） and neuraminidase （NA）. Of 16 identified HA and 9 NA subtypes, only H1N1 and H3N2 subtypes are now circulating among humans. Influenza vaccines have been available for over 60 years and well proven to be an effective public health intervention to control seasonal influenza epidemics. Seasonal influenza vaccines presently available, inactivated or split, contain the circulating strains of influenza A virus H3N2, H1N1 and influenza B virus. The composition of the vaccine is renewed semi-annually, as necessary, based on surveillance data.

关键词： influenza A virus pandemic vaccine neuraminidase cross protection

Old Master Zhu： in memory of virologist Guan-Fu Zhu

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Protein & Cell 2018年第9期9卷 749-751页

作者： qing Ye Tao Jiang cheng-feng qin Department of Virology State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071 China

Born in Dinghai County of Zhejiang province in June, 1926, Guan-Fu Zhu began to study at School of Medicine, Tongji University, in October, 1946 （Fig. 1）. Then he moved to the Department of Bacteriology and Immunology of Peking Union Medical College in September, 1954, where he got his master degree under the supervision of Prof. Shao-Wen Xie, a renowned microbiologist and immunologist. In July, 1951, Mr. Zhu served as an assistant in teaching and research section of the Second Military Medical University of PLA. In January, 1958, he began to work at the Institute of Microbi- ology and Epidemiology, Academy of Military Medical Sci- ences, successively serving as a research assistant, assistant professor, associate professor and professor. Due to cardiovascular and cerebrovascular diseases, Mr. Guan- Fu Zhu unfortunately passed away on November 7th, 2015, at the age of 89.

关键词： Virology Committee International Union Of Microbiological Societies (IUMS) Military Medical Press Honorary Chairman Common Viral Diseases

Development of Cell Lines Stably Expressing Staphylococcal Nuclease Fused to Dengue 2 Virus Capsid Protein for CTVI

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Acta Biochimica et Biophysica Sinica 2004年第8期36卷 577-582页

作者： cheng-feng qin and E-De qin Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China Institute of Microbiology and Epidemiology Academy of Military Medical SciencesBeijing 100071 China

To explore the potential application of capsid-targeted viral inactivation (CTVI) strategy in prophylactic model against dengue virus (DV) infection, here we fused a Ca2+-dependent nuclease, staphylococcal nuclease (SN), to the capsid protein of dengue 2 virus (D2C) at the carboxyl terminal, and constructed the desired expression plasmid pc/D2C-SN and control plasmids pc/D2C-SN* and pc/D2C. A mammalian cell line BHK-21 was transfected by electroporation with those plasmids and thereafter selected by 5 μg/ml blasticidin. The resistant cell clones were then expanding cultured and screened by RT-PCR and Western Blot assays. The nuclease activity of the expressed fusion protein D2C-SN was analyzed by in vitro DNA digestion assay. It was confirmed cell lines stably expressing D2C-SN and control constructs were obtained. The intracellular expressed fusion protein D2C-SN had ideal nuclease activity and no cytotoxicity on mammalian cells. Those engineered cell lines provided the experimental system for CTVI application in prophylactic model and paved the new road for combating DV infection with CTVI.

关键词： dengue 2 virus capsid protein staphylococcal nuclease CTVI stable expression

Zika virus： a new threat from mosquitoes

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Science China(Life Sciences) 2016年第4期59卷 440-442页

作者： Xiao-feng Li Jian-feng Han Pei-Yong Shi cheng-feng qin Department of Virology Beijing Institute of Microbiology and Epidemiology Beijing 100071 China. State Key Laboratory of Pathogen and Biosecurity Beijing 100071 China. Department of Biochemistry and Molecular Biology Department of Phamarcology & Toxicology Sealy Center for Structural Biology & Molecular Biophysics University of Texas Medical Branch Galveston Texas 77555 USA

In the winter of 2015,the first dengue vaccine(Dengvaxia)was approved for clinical *** virus is the most prevalent mosquito-transmitted viral pathogen in humans(qin and Shi,2014).Even though the approved Dengvaxia has... 详细信息

关键词： threat approved serotype licensed dengue Zika virus weaknesses winter vaccine transmitted

Different Gene Networks Are Disturbed by Zika Virus Infection in A Mouse Microcephaly Model

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Genomics, Proteomics & Bioinformatics 2020年第6期18卷 737-748页

作者： Yafei Chang Yisheng Jiang Cui Li qin Wang feng Zhang cheng-feng qin qing-feng Wu Jing Li Zhiheng Xu Department of Bioinformatics and Biostatistics School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Molecular Developmental Biology CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Department of Virology State Key Laboratory of Pathogen and BiosecurityBeijing Institute of Microbiology and EpidemiologyBeijing 100071China Parkinson’s Disease Center Beijing Institute for Brain DisordersBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China

The association of Zika virus(ZIKV)infection with microcephaly has raised alarm *** causal link has been confirmed in different animal models infected by ***,the molecular mechanisms underlying ZIKV pathogenesis are far from ***,we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biological and molecular networks underpinning *** found significant dysregulation of the sub-networks associated with brain development,immune response,cell death,microglial cell activation,and autophagy amongst *** provided detailed analysis of the related complicated gene networks and the links between ***,we analyzed the signaling pathways that were likely to be *** report provides systemic insights into not only the pathogenesis,but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.

关键词： Zika virus Brain development Microcephaly Gene network Signaling pathway

Convergent evolution of SARS-CoV-2 in human and animals

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Protein & Cell 2021年第11期12卷 832-835页

作者： Hang-Yu Zhou cheng-Yang Ji Hang Fan Na Han Xiao-feng Li Aiping Wu cheng-feng qin Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Suzhou Institute of Systems Medicine Suzhou 215123China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMSBeijing 100071China

Recently,many SARS-CoV-2 variants including 501Y.V1,501Y.V2 and 501Y.V3 were detected in different regions(Table S1)and drew great attention from all over the *** 501Y.V1 was firstly isolated in the United Kingdom(UK)(Davies et al.,2020)and featured with 7 substitutions including N501Y as well as 3 deletions in S *** variant was identified to increase the viral transmissibility by 56%in comparison with the preexisting *** after this report,another SARS-CoV-2 variant(501Y.V2)featured with N501Y,K417N and E484K substitutions in S protein was supposed to rapidly outcompete the preexisting strains(Tegally et al.,2020)in South ***,the 501Y.V3 variant was initially detected in Brazil and has caused rapidly increased infections with SNPs N501Y,K417T and *** them,N501Y,K417N/T and E484K are of particular interest because the N501Y was shared in all three variants and the K417N/T and E484K were detected simultaneous appeared with N501Y in 501Y.V2 and 501Y.V3.

关键词： initially evolution

Development and characterization of a clinical strain of Coxsackievirus A16 and an eGFP infectious clone

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Virologica Sinica 2015年第4期30卷 269-276页

作者： chenglin Deng Xiaodan Li Siqing Liu Linlin Xu Hanqing Ye cheng-feng qin Bo Zhang Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Chinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology

Coxsackievirus A16(CA16) is one of the major causes of hand, foot, and mouth disease(HFMD) worldwide, which is a common illness that affects children. The frequent occurrence of HFMD outbreaks has become a serious public health problem in Asia. Therefore, it is important to understand the pathogenesis and replication of CA16. In this study, a stable infectious c DNA clone of an epidemic strain of Coxsackievirus A16(CA16) was assembled, and subsequently a reporter virus(e GFP-CA16) was constructed by inserting the e GFP gene between the 5'-UTR and the N-terminus of VP4, with the addition of a 2A protease cleavage site(ITTLG) at its C-terminus. This was transfected into Vero cells to generate infectious recombinant viruses. The growth characteristics and plaque morphology, in vitro, in mammalian cells were found to be indistinguishable between the parental and recombinant viruses. Although the e GFP-CA16 showed smaller plaque size as compared to recombinant CA16, both were found to exhibit similar growth trends and EC50 of NITD008. In summary, this stable infectious c DNA clone should provide a valuable experimental system to study CA16 infection and host response. The e GFP-CA16 is expected to provide a powerful tool to monitor e GFP expression in infected cells and to evaluate the antiviral activity of potential antiviral agents in the treatment of CA16 infections.

关键词： Coxsackievirus A16(CA16) infectious cDNA clone rep

自我概念在癌症患者歧视知觉与心理社会适应间的中介效应

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现代预防医学 2024年第17期51卷 3212-3217页

作者：陈佳增翁玲玲张馨丹任丹丹黄倩李川程凤琴绵阳四〇四医院川北医学院护理学院

目的探讨癌症患者歧视知觉、自我概念和心理社会适应三者的关系，为促进癌症患者心理社会适应提供参考。方法采用便利抽样，选取四川省某市812例癌症患者，使用一般资料问卷、中文版慢性病排斥与歧视量表（CIRDS）、田纳西自我概念量... 详细信息

目的探讨癌症患者歧视知觉、自我概念和心理社会适应三者的关系，为促进癌症患者心理社会适应提供参考。方法采用便利抽样，选取四川省某市812例癌症患者，使用一般资料问卷、中文版慢性病排斥与歧视量表（CIRDS）、田纳西自我概念量表（TSCS）、疾病心理社会适应量表（PAIS-SR）调查。应用SPSS 24.0行描述性、相关性和多元线性回归分析，使用AMOS 26.0建立结构方程模型分析自我概念的中介效应，利用bootstrap验证中介效应。结果癌症患者歧视知觉总分（3.07±1.24）分、自我概念总分（206.24±46.45）分、心理社会适应总分（58.97±33.03）分。歧视知觉总分与心理社会适应总分呈正相关（r=0.503,P<0.01）；自我概念总分与心理社会适应总分、歧视知觉总分呈负相关（r=-0.506、-0.354,P<0.01）。自我概念在癌症患者歧视知觉和心理社会适应之间中介效应占比26.91%。结论癌症患者心理社会适应处于较差水平，且存在中等水平的歧视知觉和消极的自我概念。歧视知觉可直接影响癌症患者心理社会适应，也可间接通过自我概念影响心理社会适应。

关键词：癌症患者歧视知觉自我概念心理社会适应中介效应