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Truncated glycoprotein E of varicella-zoster virus is an ideal immunogen for Escherichia coli-based vaccine design

Science China(Life Sciences) 2023年第4期66卷 743-753页

作者： Tingting Chen Jie Sun Sibo Zhang Tingting Li Liqin Liu Wenhui Xue Lizhi Zhou Siting Liang Zhili Yu Qingbing Zheng Hai Yu Tong Cheng Jun Zhang Ying Gu Shaowei Li Ningshao Xia State Key laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life Sciences&School of Public HealthXiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we sought to produce a VZV g E immunogen using an E.coli expression system.We found that the soluble expression and yield of g E protein could be enhanced via C-terminal truncations to the protein,thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing.The lead truncated g E(aa 31–358),hereafter referred to as tg E,was a homogenous monomer in solution and showed excellent antigenicity.Finally,we assessed and compared the immunogenicity of tg E with commercial v Oka LAV and Shingrix vaccine.We found that aluminum-adjuvanted tg E was immunogenic as compared with v Oka LAV.When adjuvanted with AS01B,a two-dose immunization of tg E showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage,especially in terms of the proportion of IFN-γ-expressing CD4^(+)T cells.In conclusion,this method of E.coli-mediate tg E expression offers a cost-effective and scalable strategy to generate an ideal VZV g E immunogen for the development of both varicella and zoster vaccines.

关键词： varicella-zoster virus glycoprotein E Escherichia coli vaccine

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Current progress in the development of prophylactic and therapeutic vaccines

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Science China(Life Sciences) 2023年第4期66卷 679-710页

作者： Tingting Li Ciying Qian Ying Gu Jun Zhang Shaowei Li Ningshao Xia State Key laboratory of Molecular Vaccinology and Molecular Diagnostics School of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases Xiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China The Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences Xiamen 361102China

Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population.Emerging infectious diseases and outbreaks pose new challenges for vaccine development,requiring the rapid design and production of safe and effective vaccines against diseases with limited resources.Here,we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer,providing a comprehensive overview of recent advances in eight different vaccine forms(live attenuated vaccines,inactivated vaccines,polysaccharide and polysaccharide conjugate vaccines,recombinant subunit vaccines,virus-like particle and nanoparticle vaccines,polypeptide vaccines,DNA vaccines,and m RNA vaccines)and the therapeutic vaccines against five solid tumors(lung cancer,breast cancer,colorectal cancer,liver cancer and gastric cancer),three infectious diseases(human immunodeficiency virus,hepatitis B virus and human papillomavirus-induced diseases)and three common chronic diseases(hypertension,diabetes mellitus and dyslipidemia).We aim to provide new insights into vaccine technologies,platforms,applications and understanding of potential next-generation preventive and therapeutic vaccine technologies,paving the way for the vaccines design in the future.

关键词： prophylactic vaccine therapeutic vaccine immune response infectious diseases cancers chronic diseases

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Advancements in Defining and Estimating the Reproduction Number in Infectious Disease Epidemiology

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China CDC weekly 2023年第37期5卷 829-834页

作者： Kangguo Li Jiayi Wang Jiayuan Xie Jia Rui Buasiyamu Abudunaibi Hongjie Wei Hong Liu Shuo Zhang Qun Li Yan Niu Tianmu Chen State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen CityFujian ProvinceChina State Key laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamen CityFujian ProvinceChina Chinese Center for Disease Control and Prevention BeijingChina

The reproduction number(R)serves as a fundamental metric in the examination of infectious disease outbreaks,epidemics,and pandemics.Despite an array of available methods for estimating,both newcomers and established public health professionals often encounter difficulties in comprehending the circumstances for their use and their constrictions.Consequently,this review intends to offer elementary guidance on’s selection and estimation approaches.To facilitate our review,we executed an extensive search on PubMed and Web of Science applying the following search approach:[“Basic Reproduction Number/classification”(Mesh)]AND[“Basic Reproduction Number/prevention and control”(Mesh)]OR[“Basic Reproduction Number/statistics and numerical data”(Mesh)].

关键词： Basic Mesh Number

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Basic Research Advances in China on Embryo Implantation,Placentation,and Parturition

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Maternal-Fetal Medicine 2024年第1期6卷 37-49页

作者： Haili Bao Haibin Wang Fujian Provincial Key laboratory of Reproductive Health Research Department of Obstetrics and GynecologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of MedicineXiamen UniversityXiamen 361102China

This review aimed to summarize the major progress in maternal-fetal medicine achieved by Chinese scientists in recent years.PubMed was systematically searched from January 2020 to November 2023.Publications that reported the progress in embryo implantation,placentation,and parturition made by Chinese scientists in the last 3 years were selected.The milestone events during gestation,embryo implantation,endometrial decidualization,placentation,and parturition are pivotal to a successful pregnancy.Embryo implantation requires intricate interactions between implantation-competent blastocysts and receptive endometrium.To adapt to pregnancy,endometrial stromal cells transform into specialized decidual cells,which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in mice.With embryonic development,the placenta forms to support fetal growth until parturition.The maternal-fetal interface is composed of diverse cell types,including endometrial decidual cells,placental trophoblast cells,endothelial cells,and various immune cells,a sophisticated interplay among which contributes to the maintenance of pregnancy.Near term,the uterus transitions from quiescence to contractility,in preparation for delivery.Disruptions to these events lead to pregnancy-related disorders such as repeated implantation failure,recurrent pregnancy loss,preeclampsia,fetal growth restriction,preterm birth,and infertility.In recent years,Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy events.Chinese scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine research in recent years,highlighting future research directions in this field.

关键词： Embryo implantation Decidualization Placentation Maternal-fetal interface Parturition

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Trends in Respiratory Infectious Pathogens in Children Under the Age of 14—Xiamen City,Fujian Province,China,2017-2023

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China CDC weekly 2024年第8期6卷 143-147页

作者： Jiali Cao Jie Pan Xiaoqing Yang Jumei Liu Min Zhu Zeyu Zhao Ling Chen Tianmu Chen Huiming Ye Department of laboratory Medicine Fujian Key Clinical Specialty of Laboratory MedicineWomen and Children’s HospitalSchool of MedicineXiamen UniversityXiamen CityFujian ProvinceChina State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen CityFujian ProvinceChina Department of Pediatrics Women and Children's HospitalSchool of MedicineXiamen UniversityXiamen CityFujian ProvinceChina

Summary What is already known about this topic?Respiratory infections pose a significant burden on public health.Despite recent outbreaks occurring in various locations,there is limited information available on the pr... 详细信息

关键词： Xiamen spite Fujian

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表位结构指导免疫优势转移的HPV交叉疫苗的理性设计

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Science Bulletin 2024年第4期69卷 512-525页

作者：王致萍王大宁陈洁高飞江雅楠杨澄宇钱兹英池鑫张姝玥许钰洁卢一涵沈璟佳张承宗李瑾瑾周立志李婷婷郑清炳俞海李少伟夏宁邵顾颖 State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCollaborative Innovation Center of Biologic ProductsNational Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamen 361102China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China Xiamen Innovax Biotech Co. Ltd.Xiamen 361022China

In vaccine development,broadly or cross-type neutralizing antibodies(bnAbs or cnAbs)are frequently targeted to enhance protection.Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies.However,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated.In this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and HPV11.This nAb exhibited a marked preference for HPV6,demonstrating superior binding activity to virus-like particles(VLPs)and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum(90%vs.31%).Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex,we delineated the epitope as spanning four segments of amino acids(Phe42-Ala47,Gly172-Asp173,Glu255-Val275,and Val337-Tyr351)on the L1 surface loops.Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1.Substituting Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to 13H5.By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI VLPs.Remarkably,the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates.This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

关键词： Human papillomavirus Cross-neutralization antibody Immunodominance shift Vaccine design

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Epigenome-Metabolome-Epigenome signaling cascade in cell biological processes

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Journal of Genetics and Genomics 2022年第4期49卷 279-286页

作者： Linpeng Li Keshi Chen Yi Wu Ge xiang Xingguo Liu CAS Key laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Medical UniversityGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Bioland laboratory(Guangzhou Regenerative Medicine and Health Guangdong laboratory) Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesGuangzhouGuangdong 510530China c Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many years.However,the mechanisms of multilevel regulation of cell fate determination remain unclear.Recently,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell reprogramming.In this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic processes.Precise E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.

关键词： Cell biological processes Chromatin Epigenome Metabolome Signaling cascade

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Nanoparticle-based multivalent human antibodies offer potent and broad neutralization against Omicron sublineages

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3909-3912页

作者： Yizhen Wang Feibo Song Siling Wang Miaolin Lan Tingdong Li Huilin Guo Yali Zhang Shengxiang Ge Zizheng Zheng Ningshao Xia State Key laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamenChina Xiang An Biomedicine Laboratory XiamenChina and 3 Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical SciencesXiamenChina

Dear Editor As of January 2023,coronavirus disease 2019(COVID-19)induced by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused more than 6.7 million deaths,with SARS-CoV-2 variants continuing to alter the trajectory of the COVID-19 pandemic.Indeed,the prevalence of the newly emergent Omicron sublineages,particularly BA.4/5 and XBB,has highlighted the critical need for the design and production of broadly potent neutralization antibodies to efficiently combat SARS-CoV-2 variants.Neutralizing antibodies(nAbs)XMA01,XMA04,and XMA09,which target noncompeting antigenic sites in RBD(receptor binding domain),exhibit high neutralization potency against earlier disease variants(Supplementary Fig.1a–d),as previously reported by us.

关键词： antibodies acute respiratory

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Tuberculosis Prevalence Trends from a Predictive Modelling Study-10 High-Burden Countries,1980-2035

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China CDC weekly 2024年第12期6卷 225-229,I0001,I0002页

作者： Qiuping Chen Qiao Liu Kangguo Li Laurent Gavotte Roger Frutos Tianmu Chen CIRAD IntertrypMontpellierFrance Universitéde Montpellier MontpellierFrance State Key laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamen CityFujian ProvinceChina State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen CityFujian ProvinceChina Espace-Dev Universitéde MontpellierMontpellierFrance

What is already known about this topic?Given the challenges presented by drug-resistant strains of tuberculosis(TB)and the rising mobility of the population,achieving the objective of eradicating TB appears uncertain.What is added by this report?The examination of TB incidence trends in 10 highburden countries(HBCs)indicated a steady rise in cases,with India and China jointly accounting for nearly 70%of the burden.Projections for the future show diverse trajectories in these countries,with potential difficulties in reaching the TB elimination target,especially in Nigeria,Congo,and South Africa.What are the implications for public health practice?The number of TB cases is on the rise.It is crucial to learn from successful strategies to improve TB prevention and control worldwide through collaborative efforts.

关键词： tuberculosis uncertain Tuberculosis

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基于大肠杆菌表达的重组九价人乳头瘤病毒(HPV 6/11/16/18/31/33/45/52/58型)疫苗免疫原性和安全性的Ⅱ期临床试验

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Science Bulletin 2023年第20期68卷 2448-2455,M0006页

作者：胡月梅毕兆峰郑亚张黎郑凤珠储凯李亚飞陈祺全佳丽胡潇文黄兴成朱孔鑫王江雅慧姜汉民臧霞刘东林杨昌林潘红星张秋芬苏迎盈黄守杰孙光黄维金黄悦吴婷张军夏宁邵 Jiangsu Provincial Center for Disease Control and Prevention Public Health Research Institute of Jiangsu ProvinceNanjing 210009China State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsNational Innovation Platform for Industry-Education Integration in Vaccine ResearchNMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic TechnologyXiamen UniversityXiamen 361102China National Institutes for Food and Drug Control Beijing 102629China Xiamen Innovax Biotech Company Xiamen 361027China Dongtai Center for Disease Control and Prevention Yancheng 224200China

人乳头瘤病毒(HPV)16/18型双价疫苗(大肠埃希菌)已上市并通过世界卫生组织预认证.本研究通过一项随机双盲Ⅱ期临床试验评估其第二代HPV6/11/16/18/31/33/45/52/58型九价疫苗在18~45岁健康女性中的免疫原性和安全性.来自江苏省东台市的62... 详细信息

人乳头瘤病毒(HPV)16/18型双价疫苗(大肠埃希菌)已上市并通过世界卫生组织预认证.本研究通过一项随机双盲Ⅱ期临床试验评估其第二代HPV6/11/16/18/31/33/45/52/58型九价疫苗在18~45岁健康女性中的免疫原性和安全性.来自江苏省东台市的627名女性志愿者1:1随机分配至九价疫苗组(313人)或对照组(314人),并按照0、1、6月接种程序分别接种三剂1.0 mL(270μg)九价疫苗或空白佐剂,主要终点为第7月时血清抗体阳转率和抗体水平.结果显示,几乎所有疫苗组符合方案人群在第7月时出现针对9种HPV型别的血清中和抗体阳转,仅2人未发生HPV11型阳转,1人未发生HPV52型阳转.九价疫苗组和对照组的总体不良事件发生率分别为80.8%和72.9%,绝大多数不良事件症状轻微并很快恢复,未发生疫苗相关严重不良事件.该研究证明候选九价疫苗具有良好的安全性和免疫原性,支持在更大人群中进一步进行效力研究.

关键词： Ⅱ期临床试验免疫原性人乳头瘤病毒江苏省东台市双价疫苗大肠杆菌表达随机分配大肠埃希菌

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