基本信息
严景华  女  博导  中国科学院微生物研究所
电子邮件: yanjh@im.ac.cn
通信地址: 北京市朝阳区北辰西路1号
邮政编码: 100101

研究领域

结构为基础的新型疫苗及抗体工程改造


    基于结构的疫苗设计:通过对蛋白抗原结构的解析以及与抗体相互作用研究,分析抗原结构特征,设计结构完整有效疫苗。这种策略能够最大限度的保证抗原表位的空间结构,从而提高疫苗的免疫源性。

   抗体药物作用机制及抗体药物研发:抗体药物在治疗肿瘤、自身免疫性疾病、传染病等领域取得了突破性进展,在全球销售额前十位药物中,抗体药物占据六席,抗体药物正以前所未有的速度快速发展。本实验室研究内容之一就是利用抗体筛选平台及结构生物学平台研究抗体药物的作用机制,并进一步开发新的抗体药物。

   人源抗体筛选及动物来源抗体的人源化:利用噬菌体展示、酵母展示及人B细胞单细胞测序技术筛选重要传染病及肿瘤治疗性人源抗体。另外对鼠等动物来源抗体进行人源化改造。



招生信息

   
招生专业
071010-生物化学与分子生物学
招生方向
抗体药物作用机制研究及治疗性抗体药物研发
基于蛋白质结构的新型疫苗设计及研发
结构为基础的新型疫苗设计、抗体筛选及作用机制研究

教育背景

2001-09--2004-07   中国人民解放军军事医学科学院生物工程研究所   博士
1986-09--1989-07   南京农业大学农学系   硕士
1982-09--1986-07   安徽师范大学生物系   学士

工作经历

   
工作简历
2012-07~现在, 中国科学院微生物研究所, 研究员
2004-07~2012-07,中国科学院微生物研究所, 副研究员
1989-07~2001-08,安徽农业大学, 讲师 副教授
社会兼职
2021-12-21-今,Trends in Microbiology, 顾问
2021-02-19-今,Journal of Genetics and Genomics, 编委
2019-01-01-今,北京医学会医学病毒学分会, 委员
2018-12-29-今,Biosafety and Health, 编委
2018-07-01-今,《科学通报》, 编委
2018-04-13-今,中国生物工程学会抗体专业委员会(筹), 主任委员
2017-11-01-今,中国工程学会精准医疗与伴随诊断专业会员会, 副主任委员

教授课程

生物药物研究与开发
分子病毒学
免疫治疗
重大慢性传染病
微生物学实验技术

专利与奖励

   
奖励信息
(1) 领雁银奖·振翅奖, 研究所(学校), 2021
(2) 中国科学院微生物研究所所长奖教金特别奖, 特等奖, 研究所(学校), 2021
(3) 中国科学院优秀导师奖, 院级, 2021
(4) 中国科学院优秀导师奖, 院级, 2020
(5) 抗击新冠肺炎疫情全国三八红旗集体, 国家级, 2020
(6) 全国抗击新冠肺炎疫情先进个人, , 国家级, 2020
(7) 全国创新争先奖, , 国家级, 2020
(8) “求是”杰出成就集体奖, , 其他, 2019
(9) 禽流感病毒感染人的生态与分子机制研究, 一等奖, 部委级, 2017
(10) 中国生命科学领域十大进展, 部委级, 2016
(11) 我国新现超强致病链球菌跨种传播致中毒性休克机制破解和侦检防, 二等奖, 国家级, 2014

出版信息

   
发表论文
(1) A non-ACE2-blocking neutralizing antibody against Omicron-included SARS-CoV-2 variants, Signal Transduction and Targeted Therapy, 2022, 
(2) Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants, Emerging Microbes & Infections, 2022, 
(3) Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials, LANCET INFECTIOUS DISEASES, 2021, 
(4) Distinct BCR repertoires elicited by SARS-CoV-2 RBD and S vaccinations in mice, CELL DISCOVERY, 2021, 通讯作者
(5) COVID-19 mRNA vaccines, JOURNAL OF GENETICS AND GENOMICS, 2021, 通讯作者
(6) Molecular basis of pangolin ACE2 engaged by COVID-19 virus, CHINESE SCIENCE BULLETIN-CHINESE, 2021, 第 6 作者
(7) Cross-species recognition of SARS-CoV-2 to bat ACE2, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 第 15 作者
(8) A single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2, NATURE COMMUNICATIONS, 2021, 通讯作者
(9) A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants, NATURE COMMUNICATIONS, 2021, 通讯作者
(10) Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch, NATURE IMMUNOLOGY, 2021, 通讯作者
(11) Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants, NATURE COMMUNICATIONS, 2021, 第 20 作者
(12) Nanozyme chemiluminescence paper test for rapid and sensitive detection of SARS-CoV-2 antigen, BIOSENSORS & BIOELECTRONICS, 2021, 第 7 作者
(13) SARS-CoV-2 virus: Vaccines in development, Fundamental Research, 2021, 通讯作者
(14) Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab, in Chinese Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2021, 第 19 作者
(15) PD-1的FG环是肿瘤免疫检查点治疗中单克隆抗体的“热点”, The FG Loop of PD-1 Serves as a"Hotspot"for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy, 科学新闻, 2020, 第 27 作者
(16) The identification of a CD47-blocking "hotspot" and design of a CD47, Signal Transduction and Targeted Therapy, 2020, 第 10 作者
(17) Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex, CELLULAR & MOLECULAR IMMUNOLOGY, 2020, 第 13 作者
(18) Identification of a hotspot on PD-L1 for pH-dependent binding by monoclonal antibodies for tumor therapy, Identification of a hotspot on PD-L1 for pH-dependent binding by monoclonal antibodies for tumor therapy, SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2020, 通讯作者
(19) The structural basis of African swine fever virus pA104R binding to DNA and its inhibition by stilbene derivatives, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 第 9 作者
(20) A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS, CELL, 2020, 通讯作者
(21) 新型冠状病毒结合穿山甲ACE2受体的分子机制, 科学通报, 2020, 第 6 作者
(22) The identification of a CD47-blocking"hotspot"and design of a CD47/PD-L1 dual-specific antibody with limited hemagglutination, The identification of a CD47-blocking "hotspot" and design of a CD47/PD-L1 dual-specific antibody with limited hemagglutination, SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2020, 通讯作者
(23) A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS, Cell, 2020, 第 20 作者
(24) N-glycosylation of PD-1 promotes binding of camrelizumab, EMBO REPORTS, 2020, 第 8 作者
(25) Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2, CELL DISCOVERY, 2020, 通讯作者
(26) Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species, JOURNAL OF VIROLOGY, 2020, 第 6 作者
(27) Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry, EMERGING MICROBES & INFECTIONS, 2020, 第 13 作者
(28) Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant, ADVANCED MATERIALS, 2020, 第 6 作者
(29) Molecular basis of EphA2 recognition by gHgL from gammaherpesviruses, NATURE COMMUNICATIONS, 2020, 通讯作者
(30) A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2, NATURE, 2020, 通讯作者
(31) Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2, CELL, 2020, 通讯作者
(32) The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy, ISCIENCE, 2019, 通讯作者
(33) Double Lock of a Human Neutralizing and Protective Monoclonal Antibody Targeting the Yellow Fever Virus Envelope, CELL REPORTS, 2019, 第 14 作者
(34) Cryo-EM Structure of the African Swine Fever Virus, CELL HOST & MICROBE, 2019, 第 17 作者
(35) Structural insight into RNA synthesis by influenza D polymerase, NATURE MICROBIOLOGY, 2019, 其他(合作组作者)
(36) Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein, CELL, 2019, 第 15 作者
(37) Neutralization mechanism of human monoclonal antibodies against rift valley fever virus, NATURE MICROBIOLOGY, 2019, 通讯作者
(38) Novel l,3,5-thiadiazine-2-thione derivatives containing a hydrazide moiety: Design, synthesis and bioactive evaluation against phytopathogenic fungi in vitro and in vivo, Chinese Chemical Letters, 2019, 第 5 作者
(39) 基于非结构蛋白1(NS1)的黄病毒感染诊断研究进展, Progress in Non-structural Protein 1 (NS1) Based Diagnosis of Flaviviruses Infection, 中国生物工程杂志, 2019, 第 2 作者
(40) Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses, CELL DISCOVERY, 2019, 第 18 作者
(41) Novel 1,3,5-thiadiazine-2-thione derivatives containing a hydrazide moiety: Design, synthesis and bioactive evaluation against phytopathogenic fungi in vitro and in vivo, CHINESE CHEMICAL LETTERS, 2019, 第 5 作者
(42) Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy, MABS, 2019, 通讯作者
(43) Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B, CELL, 2019, 第 24 作者
(44) Novel 1,3,5-thiadiazine-2-thione derivatives containing a hydrazide moiety: Design, synthesis and bioactive evaluation against phytopathogenic fungi in vitro and in vivo, Novel 1,3,5-thiadiazine-2-thione derivatives containing a hydrazide moiety: Design, synthesis and bioactive evaluation against phytopathogenic fungi in vitro and in vivo, 中国化学快报:英文版, 2019, 第 5 作者
(45) Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin, CELL REPORTS, 2019, 第 13 作者
(46) Noc4L-Mediated Ribosome Biogenesis Controls Activation of Regulatory and Conventional T Cells, CELL REPORTS, 2019, 第 7 作者
(47) Limited Cross-Linking of 4-1BB by 4-1BB Ligand and the Agonist Monoclonal Antibody Utomilumab, CELL REPORTS, 2018, 第 15 作者
(48) 单细胞测序技术及其在传染病研究领域中的应用, Single-cell sequencing technology and its application in infectious disease, 生物产业技术, 2018, 第 2 作者
(49) Clinical, immunological and bacteriological characteristics of H7N9 patients nosocomially co-infected by Acinetobacter Baumannii: a case control study, BMC INFECTIOUS DISEASES, 2018, 第 13 作者
(50) Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells, JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 第 17 作者
(51) Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses, MBIO, 2018, 第 17 作者
(52) Endogenous Cellular MicroRNAs Mediate Antiviral Defense against Influenza A Virus, MOLECULAR THERAPY-NUCLEIC ACIDS, 2018, 第 8 作者
(53) Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage, JOURNAL OF VIROLOGY, 2018, 第 17 作者
(54) Natural killer cells are activated and play a protective role against ZIKA virus infection in mice, SCIENCE BULLETIN, 2017, 第 10 作者
(55) CASCIRE Surveillance Network and Work on Avian Influenza Viruses, SCIENCE CHINA-LIFE SCIENCES, 2017, 第 29 作者
(56) Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains, NATURE COMMUNICATIONS, 2017, 第 9 作者
(57) Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D, PLOS PATHOGENS, 2017, 
(58) Targeted disruption of Noc4l leads to preimplantation embryonic lethality in mice, PROTEIN & CELL, 2017, 第 4 作者
(59) Both structure and function of human monoclonal antibodies contribute to enhancement of Zika virus infectivity in vitro, SCIENCE CHINA-LIFE SCIENCES, 2017, 第 6 作者
(60) Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for Vaccine Design, JOURNAL OF VIROLOGY, 2017, 第 2 作者
(61) Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy., CELL RESEARCH, 2017, 其他(合作组作者)
(62) Remarkably similar CTLA-4 binding properties of therapeutic ipilimumab and tremelimumab antibodies, ONCOTARGET, 2017, 第 7 作者
(63) The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection, VACCINE, 2017, 第 7 作者
(64) An unexpected N-terminal loop in PD-1 dominates binding by nivolumab, NATURE COMMUNICATIONS, 2017, 通讯作者
(65) CTL immunogenicity of Rv3615c antigen and diagnostic performances of an ESAT-6/CFP-10/Rv3615c antigen cocktail for Mycobacterium tuberculosis infection, TUBERCULOSIS, 2017, 第 15 作者
(66) Hemagglutinin-specific CD4+ T-cell responses following 2009-pH1N1 inactivated split-vaccine inoculation in humans, VACCINE, 2017, 第 10 作者
(67) Bacterial effector NleL promotes enterohemorrhagic E. coli -induced attaching and effacing lesions by ubiquitylating and inactivating JNK, PLOS PATHOGENS, 2017, 第 16 作者
(68) Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model, ANTIVIRAL RESEARCH, 2017, 第 14 作者
(69) Putative Receptor Binding Domain of Bat-Derived CoronavirusHKU9 Spike Protein: Evolution of Betacoronavirus Receptor BindingMotifs, BIOCHEMISTRY, 2016, 第 8 作者
(70) MERS-CoV spike protein: Targets for vaccines and therapeutics, ANTIVIRAL RESEARCH, 2016, 第 4 作者
(71) Structural basis of collagen recognition by human osteoclast-associated receptor and design of osteoclastogenesis inhibitors, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 第 6 作者
(72) Molecular Basis of Antibody-Mediated Neutralization and Protection Against Flavivirus, IUBMB LIFE, 2016, 第 5 作者
(73) Cross-immunity Against Avian Influenza A(H7N9) Virus in the Healthy Population Is Affected by Antigenicity-Dependent Substitutions, JOURNAL OF INFECTIOUS DISEASES, 2016, 第11作者
(74) Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus, PLOS NEGLECTED TROPICAL DISEASES, 2016, 其他(合作组作者)
(75) Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection, JOURNAL OF IMMUNOLOGY, 2016, 第 7 作者
(76) Structural and functional analysis of an anchorless fibronectin-binding protein FBPS from Gram-positive bacterium Streptococcus suis, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 其他(合作组作者)
(77) Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1, CELL, 2016, 第 6 作者
(78) Structure-based tetravalent zanamivir with potent inhibitory activity against drug-resistant influenza viruses, JOURNAL OF MEDICINAL CHEMISTRY, 2016, 第 10 作者
(79) Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody, CELL HOST & MICROBE, 2016, 其他(合作组作者)
(80) Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies, PROTEIN & CELL, 2016, 第 10 作者
(81) Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus, SCIENCE TRANSLATIONAL MEDICINE, 2016, 
(82) Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies, Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies, 蛋白质与细胞:英文版, 2016, 第 10 作者
(83) The NS1 gene from bat-derived influenza-like virus H17N10 can be rescued in influenza A PR8 backbone, JOURNAL OF GENERAL VIROLOGY, 2016, 第 7 作者
(84) Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus, JOURNAL OF VIROLOGY, 2016, 第11作者
(85) Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice, CELL, 2016, 其他(合作组作者)
(86) 埃博拉病毒入侵: 人TIM分子的结构与结合PS的分子基础, Crystal structures of human TIM members: Ebolavirus entry-enhancing receptors, 科学通报, 2015, 其他(合作组作者)
(87) Distribution of sialic acid receptors and experimental infections with different subtypes of influenza A viruses in Qinghai-Tibet plateau wild pika, VIROLOGY JOURNAL, 2015, 第 13 作者
(88) 人单核细胞系中HIV-1前病毒转录调节新型研究模型的建立, 微生物学通报, 2015, 第 5 作者
(89) A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein, CELL RESEARCH, 2015, 通讯作者
(90) A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein, CELL RESEARCH, 2015, 通讯作者
(91) Adaptation of avian influenza A (H6N1) virus from avian to human receptor-binding preference, EMBO JOURNAL, 2015, 第 9 作者
(92) Distribution of sialic acid receptors and experimental infections with different subtypes of influenza A viruses in Qinghai-Tibet plateau wild pika, 2015, 
(93) MicroRNAs: the novel targets for Ebola drugs, SCIENCE CHINA-LIFE SCIENCES, 2014, 通讯作者
(94) Continuous reassortments with local chicken H9N2 virus underlie the human-infecting influenza A (H7N9) virus in the new influenza season, Guangdong, China, Continuous reassortments with local chicken H9N2 virus underlie the human-infecting influenza A (H7N9) virus in the new influenza season, Guangdong, China, 蛋白质与细胞:英文版, 2014, 第 7 作者
(95) PILRα and PILRβ have a siglec fold and provide the basis of binding to sialic acid, Proceedings of the National Academy of Sciences of the United States of America, 2014, 
(96) PILR alpha and PILR beta have a siglec fold and provide the basis of binding to sialic acid, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 第11作者
(97) Analysis of Influenza Virus Receptor Specificity Using Glycan-Functionalized Gold Nanoparticles, ACS NANO, 2014, 其他(合作组作者)
(98) Characterization of the Nucleocytoplasmic Shuttle of the Matrix Protein of Influenza B Virus, JOURNAL OF VIROLOGY, 2014, 第 7 作者
(99) Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability, SCIENTIFIC REPORTS, 2014, 第 6 作者
(100) Bat Origins of MERS-CoV Supported by Bat Coronavirus HKU4Usage of Human Receptor CD26, CELL HOST & MICROBE, 2014, 第 14 作者
发表著作
(1) 寨卡病毒与之寨卡病毒病-预防与治疗用抗体, 人民卫生出版社, 2019-05, 第 1 作者

科研活动

   
参与会议
(1)SARS-CoV-2 中和抗体表位与疫苗设计   2022年病原组学专题研讨会   2022-01-15
(2)SARS-CoV-2 中和抗体表位特征与疫苗设计   中关村论坛 “第二届全球科学与生命健康论坛”    2021-09-25
(3)新冠mRNA疫苗抗原设计和BCR谱   NID 2021核酸药物产业发展论坛   2021-09-23
(4)SARS-CoV-2 中和抗体表位与疫苗设计   中国疫苗行业协会   2021-04-21
(5)新冠病毒重组蛋白疫苗安全性有效性介绍   国务院联防联控机制新闻发布会   2021-03-21
(6)中和抗体:抗击新发再发传染病的重要手段   2020云端未来科学大奖周-生命与健康论坛   2020-12-29
(7)新冠疫苗与抗体药物研发进展   首届中国卫生健康科技创新发展大会   2020-11-27
(8)新冠病毒重组蛋白疫苗研究进展   中国生物制品年会   2020-11-20
(9)COVID-19重组蛋白研究进展   中国生物技术创新大会   2020-11-04
(10)新冠疫情中的抗体研发、产业化生产和临床试验系统性工作   微生物遗传前言交叉云端论坛   2020-09-19
(11)流感等病毒疫苗研发进展   全国流感监测与防控工作年会   2020-09-10
(12)感染性疾病的多特异性抗体治疗研发   2020第四届免疫基因及细胞治疗论坛   2020-09-01
(13)SARS-CoV-2中和抗体研发(Neutralizing mAbs for SARS-CoV-2)   美国华人生物医药科技协会年会   2020-08-29
(14)病毒疫苗的研发途径   2020中国医学会儿科学分会学术年会呼吸组   2020-07-18
(15)介绍新冠肺炎疫情相关科学研究情况,答记者问   国务院新闻办公室吹风会   2020-04-27
(16)疫苗研发策略及进展    国务院新冠肺炎疫情联防联控机制新闻发布会   2020-02-15