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个人简介

何放,浙江大学动物科学学院“百人计划”研究员,博士生导师。长期从事传染病原疫苗和抗体的研制和功能研究,主要对象包括各类流感病毒(包括高致病禽流感H5N1,H7N9等)、EV71肠道病毒和各类重大猪病病毒。自2003年非典肺炎SARS爆发起,从事重大人畜共患传染病原研究工作,有多年高等级生物安全实验室工作经验。2010-2016期间,担任新加坡首个P3(生物安全三级)实验室主任。回国后的工作重点是借助各类重大猪病病毒的动物感染模型,解析免疫和病毒对抗机制,在此基础上全方位研发及改良疫苗和其他新型抗病毒策略。 学术成绩: 发表SCI论文45篇,其中26篇为通讯作者或第一作者,累计影响因子超过150,发表期刊包括本领域内顶级期刊,包括Journal of Virology,Journal of Immunology,PNAS等。另获授权国际发明专利8项,全部有关于抗病毒抗体和疫苗的研制。 创新成果: A.建立新型亚单位疫苗表达体系。多方面策略提升新型亚单位抗原构象匹配度和表达量,以达到更良好的准确的免疫原性,同时引入纳米颗粒形式及佐剂共表达等方式,提升亚单位疫苗细胞免疫和先天免疫的诱导能力,在保留亚单位疫苗高安全性的优势基础上,打破传统观念中亚单位疫苗功效单一的局限。 B.高水平抗体免疫应答提升策略。制备各种重大病毒的新型高效中和抗体、广谱抗体和双表位抗体,设计新型多功能免疫诊断方法,实现对多种重要人畜共患病原的有效抗体治疗和灵敏通用诊断。 C.广谱疫苗的机制研究和应用评价。立足抗原免疫原性的精确化分析,实现疫苗通用保护功效。通过对抗原表位的种类、分布和进化规律统计,实现各类H5N1广谱疫苗和通用抗体的研制与开发。相关技术转让美国上市公司Emergent Biosolution和新加坡国家农粮局等集团机构进行产品转化,也应用于H5、H7等的快速精确灵敏诊断试剂盒的构建。 D.新型特色猪病疫苗研究和紧密的产学研合作。主要成果包括:猪瘟病毒E2单位纳米颗粒疫苗的研制和优化;猪圆环病毒2型CAP佐剂嵌合疫苗的研制;猪繁殖和呼吸综合征病毒新型疫苗株的筛选和构建等。力图运用对动物病毒的研究机制反馈启发推动对人畜共患病原新型抗病毒策略的研制。将前期对人类病毒的研究方案,转化应用于猪病的疫苗研制和机制研究。力图在我国动物保健产业,引入医学相关最尖端技术,研发高质量高精细疫苗,结合实际平衡成本。同时利用动物病毒低风险的研究平台揭示病毒的新型调控机制,服务启迪推进人类重大病毒相关研究的进程。 教育经历 学位 起始时间 终止时间 院校 专业 学士 1999.9 2003.6 上海交通大学 生物技术 博士 2004.1 2009.12 新加坡国立大学 分子病毒学 工作经历 起始时间 终止时间 单位 职务 2003.7 2003.12 新加坡淡马锡生命科学研究院 研究助理 2010.1 2013.3 新加坡淡马锡生命科学研究院 博士后 2013.4 2015.3 新加坡淡马锡生命科学研究院 战略科研主任 2015.4 2016.1 新加坡淡马锡生命科学研究院 Principal Investigator 2016.2 至今 浙江大学 研究员 教学与课程 动物卫生法规 生物医药工程专题 动物免疫学 兽医分子病理生物学 生物制品学 实验室建设 序号 专利名称 专利号 批准时间 申请 (国家)地区 1 Monoclonal antibodies specific to hemagglutinin and neuraminidase from influenza virus H5-subtype or N1-subtype and uses thereof 8540996 2013.02.06 美国 2 H5 subtype-specific binding proteins useful for H5 avian influenza diagnosis and surveillance 8637644 2014.01.28 美国 3 Monoclonal antibody specific to major neutralizing epitope of influenza H5 hemagglutinin 8992929 2015.03.31 美国 4 Monoclonal antibodies specific to hemagglutinin from influenza virus H5-subtype and uses thereof 9115188 2015.08.25 美国 5 Monoclonal antibodies targeting neutralizing epitopes on h5 influenza virus of clade 2.3 9233152 2016.01.12 美国 6 Universal vaccine against H5N1 lineages 9555093 2017.01.31 美国 7 Monoclonal antibodies targeting neutralizing epitopes on h7 influenza viruses 9637537 2017.05.02 美国 8 Monovalent H5 Vaccine 9694067 2017.07.04 美国 自2013年成立独立的科研团队,有丰富的管理经验和开放的实验室管理模式,重在素质培养和事业发展导向,主张产学研一体的研究生培养方向。

研究领域

新型亚单位疫苗和纳米颗粒疫苗的研制和应用 新型抗体研发与机制研究 宿主疫苗免疫应答的提升和优化 病毒感染与宿主免疫对抗机制研究

近期论文

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Publication*通讯作者 Huiling Xu,Guangwei Han,Ying Lu,Zehui Liu,Lina Tao,He Fang*.(2021)Broad neutralization of CSFV with novel monoclonal antibodies in vivo.Int J Biol Macromol.2021 Jan 23;173:513-523.doi:10.1016/j.ijbiomac.2021.01.142.(IF5=5.137) Xu HL,Liu Ze-Hui.,Zheng Suya,Han Guangwei.,He Fang*.(2020).CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression.Vaccines(Basel).2020 8(4),592;https://doi.org/10.3390/vaccines8040592(IF4.105) Tao LN,Liu ZH,Xu HL,Lu Y,Liao M,He Fang*.(2020).LvYY1 Activates WSSV ie1 Promoter for Enhanced Vaccine Production and Efficacy.Vaccines(Basel).2020 Sep 8;8(3):E510.doi:10.3390/vaccines8030510.PMID:32911686(IF4.105) Han Guangwei.,Xu Huiling.,Wang Yanli.,Liu Zehui.,He Fang*.(2020).Efficacy Evaluation of Two Commercial Vaccines Against a Recombinant PRRSV2 Strain ZJnb16-2 From Lineage 8 and 3 in China.Pathogens,9(1),(IF3.405)doi:10.3390/pathogens9010059 Xu H,Wang Y,Han G,Fang W,He Fang*.(2020)Identification of E2 with improved secretion and immunogenicity against CSFV in piglets.BMCMicrobiol.2020;20(1):26.Published2020Feb4.(IF3.287)doi:10.1186/s12866-020-1713-2 Han Guangwei.,Lei Kaixia.,Xu Huiling.,He Fang*.(2020).Genetic characterization of a novel recombinant PRRSV2 from lineage 8,1 and 3 in China with significant variation in replication efficiency and cytopathic effects.Transbound Emerg Dis,2020 Jul;67(4):1574-1584.doi:10.1111/tbed.13491.Epub 2020 Feb 5..(IF4.188)doi:10.1111/tbed.13491 Liu Ze-Hui.,Lei Kai-Xia.,Han Guang-Wei.,Xu Hui-Ling.,He Fang*.(2020).Novel Lentivirus-Based Method for Rapid Selection of Inhibitory Nanobody against PRRSV.Viruses,12(2)(IF 3.811)doi:10.3390/v12020229 Han Guangwei.,Xu Huiling,Wang Kexiong,He Fang*.(2019).Emergence of Two different recombinant PRRSV strains with low neutralizing antibody susceptibility in China.Sci Rep,9(1),2490.(IF4.011)doi:10.1038/s41598-019-39059-8 Li Liang.,etc.,He Fang.,Kwong Chow Vincent Tak.,Tan Nguan Soon.(2019).Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia.mBio,10(3),undefined.(IF6.747)doi:10.1128/mBio.02469-18 Pierce Carrie L.,Williams Tracie L.,Santana Wanda I.,Levine Marnie.,Chen Li-Mei.,Cooper Hans C.,Solano Maria I.,Woolfitt Adrian R.,Marasco Wayne A.,Fang He.,Donis Ruben O.,Barr John R.(2017).Immunocapture isotope dilution mass spectrometry in response to a pandemic influenza threat.Vaccine,35(37),5011-5018.(IF3.269)doi:10.1016/j.vaccine.2017.07.049 Jia Q,Ng Q,Chin W,Meng T,Chow VTK,Wang CI,Kwang J,He F*.Effective in vivo therapeutic IgG antibody against VP3 of enterovirus 71 with receptor-competing activity.Sci Rep.2017 Apr 19;7:46402.doi:10.1038/srep46402. He Fang*.,Leyrer Sonja.,Kwang Jimmy.(2016).Strategies towards universal pandemic influenza vaccines.Expert Rev Vaccines,15(2),215-25.(IF4.531)doi:10.1586/14760584.2016.1115352 Ng Qingyong.,He Fang*,Kwang Jimmy*.(2015).Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines.Viruses,7(12),6441-57.(IF3.811)doi:10.3390/v7122949 Tan Y,He Fang*and Kwang J.*(2015)How can we develop universal H5N1 vaccines Immunotherapy 2015 Aug 7:1-4 P.Rai,M.Parrish,I.J.J.Tay,L.Na,S.Ackerman,He F.,J Kwang,V.T.K.Chow and B.P.Engelward.(2015)Streptococcus pneumoniae Secretes Hydrogen Peroxide Leading to DNA Damage and Apoptosis in Lung Cells.PNAS 112(26):E342130 Rai P,He F,Kwang J,Engelward BP,Chow VT.Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest.Sci Rep.2016 Mar 30;6:22972.doi:10.1038/srep22972. Kumar SR,Prabakaran M,K.V.Ashok Raj,He F.and J.Kwang(2015)Amino acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge PLoS One 10(6):e0128940 Tan Y,Ng QY,Jia Q,Kwang J and He Fang*.(2015)A novel humanized antibody neutralizes H5N1 via two different mechanisms..J Virol 89(7):3712-22 He,F.,Prabakaran M,Kumar SR,Tan Y,Kwang J.(2014)Monovalent H5 vaccine based on epitope-chimeric HA provides broad cross-clade protection against variant H5N1 viruses in mice.Antiviral Research.105:143-151. Prabakaran,M.,Leyrer S.,He F.,Auer S.,S.R Kumar,Kindsmueller K.,Mytle N.,Schneider J.,Lockhart S.,Kwang J..(2014)Progress Toward A Universal H5N1 Vaccine:A Recombinant Modified Vaccina Virus Ankara-expressing Trivalent Hemagglutinin Vaccine.PLoS ONE 17;9(9):e107316. Prabakaran,M.,S.Rajesh Kumar,K.V.Ashok Raj,X.Wu,He F..,J.Zhou,and J.Kwang.(2014).Cross-protective efficacy of baculovirus displayed hemagglutinin against highly pathogenic influenza H7 subtypes.Antiviral Res 109C:149-159. He,F.,Prabakaran M,Tan Y,Indira K,Kumar SR,Kwang J.(2013)Development of dual-function ELISA for effective antigen and antibody detection against H7 avian influenza virus.BMC Microbiol.2013 Oct 2;13(1):219. He,F.,S.R.Kumar,et al.(2013)Effective intranasal therapeutics and prophylactics with monoclonal antibody against lethal infection of H7N7 influenza virus.Antiviral Research.100(1):207-14 He,F and Kwang J.(2013)Monoclonal antibody targeting neutralizing epitope on H5N1 influenza virus of clade 1 and 0 for specific H5 quantification.Influenza Research and Treatment 2013;2013:360675.doi:10.1155/2013/360675. He,F.,T.K.Kiener,et al.(2013).Development of a sensitive and specific epitope-blocking ELISA for universal detection of antibodies to human enterovirus 71 strains.PLoS One 8(1):e55517. Prabakaran,M.,A.B.Kolpe,He,F.,et al.(2013).Cross-protective efficacy of bivalent recombinant baculoviral vaccine against heterologous influenza H5N1 challenge.Vaccine 31(10):1385-1392. Chen,Q.,He F.,et al.(2012).GM-CSF and IL-4 stimulate antibody responses in humanized mice by promoting T,B,and dendritic cell maturation.J Immunol 189(11):5223-5229. Kiener TK,Jia Q,Lim XF,He F,Meng T,et al.(2012)Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein.Virol J 9:55. He,F and Kwang J.(2011)Universal Recognition and Vaccination of H5N1 Hemagglutinin.Asia Pacific Biotech News 15(11),19-22 Velumani S,Ho HT,He F,Musthaq S,Prabakaran M,et al.(2011)A novel peptide ELISA for universal detection of antibodies to human H5N1 influenza viruses.PLoS One 6:e20737. Prabakaran M,Meng T,He F,Yunrui T,Qiang J,et al.(2011)Subcutaneous immunization with baculovirus surface-displayed hemagglutinin of pandemic H1N1 Influenza A virus induces protective immunity in mice.Clin Vaccine Immunol 18:1582-1585. He,F.,Retno,D S.,Sri,M.,Goutama,M.and Kwang,J.(2010).Complementary monoclonal antibody-based dot ELISA for universal detection of H5 avian influenza virus.BMC Microbiol 10,330 Prabakaran,M,He F,T Meng,S Madhan,Y Tan,Q Jia and J Kwang.2010.Neutralizing Epitopes of Influenza Virus Hemagglutinin:Target for the Development of a Universal Vaccine against H5N1 Lineages.J Virol 84:11822-11830. Chua,TH,CYH Leung,He F,CK Chow,SK Ma,SF Sia,IHY Ng,SG Fenwick,CM James,SB Chua,ST Chew,J Kwang,JSM Peiris and TM Ellis.2010.Evaluation of a Subunit H5 Vaccine and an Inactivated H5N2 Avian Influenza Marker Vaccine in Ducks Challenged with Vietnamese H5N1 Highly Pathogenic Avian Influenza Virus.Influenza Research and Treatment 2010,Article ID 489213. He,F.,Madhan,S.,and Kwang,J.(2009).Baculovirus vector as a delivery vehicle for influenza vaccines.Expert Rev Vaccines 8(4),455-67. He,F.,Du,Q.,Ho,Y.,and Kwang,J.(2009).Immunohistochemical detection of Influenza virus infection in formalin-fixed tissues with anti-H5 monoclonal antibody recognizing FFWTILKP.J Virol Methods 155(1),25-33. He,F.,Syed,S.M.,Hameed,A.S.,and Kwang,J.(2009).Viral ubiquitin ligase WSSV222 is required for efficient white spot syndrome virus(WSSV)replication in shrimp.J Gen Virol 90(pt6),1483-90. Ho,H.T.,Qian,H.L.,He,F.,Meng,T.,Szyporta,M.,Prabhu,N.,Prabakaran,M.,Chan,K.P.,and Kwang,J.(2009).Rapid detection of H5N1 subtype influenza viruses by antigen capture enzyme-linked immunosorbent assay using H5-and N1-specific monoclonal antibodies.Clin Vaccine Immunol 16(5),726-32. Prabhu,N.,Prabakaran,M.,He,F.,Qian,H.L.,Ho,H.T.,Jia,Q.and Kwang,J.(2009)Combination Therapy using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents formation of Escape Mutants.PLoS ONE 4(5),e5672. Prabakaran,M.,Ho,H.T.,Prabhu,N.,Velumani,S.,Szyporta,M.,He,F.,Chan,K.P.,Chen,L.M.,Matsuoka,Y.,Donis,R.O.,and Kwang,J.(2009).Development of epitope-blocking ELISA for universal detection of antibodies to human H5N1 influenza viruses.PLoS ONE 4(2),e4566. Prabhu,N,M Prabakaran,Qian HL,He F,H Ho,J Qiang,M Goutama,A P Lim,BJ Hanson and J Kwang.(2009)Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 hemagglutinin against lethal H5N1 Influenza.Antiviral therapy,14:911-921. He,F.,and Kwang,J.(2008).Identification and characterization of a new E3 ubiquitin ligase in white spot syndrome virus involved in virus latency.Virol J 5,151. He,F.,Ho,Y.,Yu,L.,and Kwang,J.(2008).WSSV ie1 promoter is more efficient than CMV promoter to express H5 hemagglutinin from influenza virus in baculovirus as a chicken vaccine.BMC Microbiol 8,238. Prabakaran,M.,Velumani,S.,He,F.,Karuppannan,A.K.,Geng,G.Y.,Yin,L.K.,and Kwang,J.(2008).Protective immunity against influenza H5N1 virus challenge in mice by intranasal co-administration of baculovirus surface-displayed HA and recombinant CTB as an adjuvant.Virology 380(2),412-20. Liu,J.,Zhu,Y.,Chen,I.,Lau,J.,He,F.,Lau,A.,Wang,Z.,Karuppannan,A.K.,and Kwang,J.(2007).The ORF3 protein of porcine circovirus type 2 interacts with porcine ubiquitin E3 ligase Pirh2 and facilitates p53 expression in viral infection.J Virol 81(17),9560-7. He,F.,Fenner,B.J.,Godwin,A.K.,and Kwang,J.(2006).White spot syndrome virus open reading frame 222 encodes a viral E3 ligase and mediates degradation of a host tumor suppressor via ubiquitination.J Virol 80(8),3884-92. Wang,Z.,Chua,H.K.,Gusti,A.A.,He,F.,Fenner,B.,Manopo,I.,Wang,H.,and Kwang,J.(2005).RING-H2 protein WSSV249 from white spot syndrome virus sequesters a shrimp ubiquitin-conjugating enzyme,PvUbc,for viral pathogenesis.J Virol 79(14),8764-72.

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