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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou Yuqiong Que Tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia state key laboratory of molecular vaccinology and molecular diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China national institute of diagnostics and vaccine development in infectious diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China state key laboratory of vaccines for infectious diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine laboratory Xiamen 361102China institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or vaccination.The rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus strain.Here,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron subvariants.Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing.Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5.Together,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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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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A review of the safety and efficacy of current COVID-19 vaccines

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Frontiers of Medicine 2022年第1期16卷 39-55页

作者： Zehong Huang Yingying Su Tianying Zhang Ningshao Xia state key laboratory of molecular vaccinology and molecular diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesStrait Collaborative Innovation Center of Biomedicine and PharmaceuticsSchool of Public HealthXiamen UniversityXiamen 361102China

Vaccination is the most effective and feasible way to contain the coronavirus disease 2019(COVID-19)pandemic.The rapid development of effective COVID-19 vaccines is an extraordinary achievement.This study reviewed the efficacy/effectiveness,immunogenicity,and safety profile of the 12 most progressed COVID-19 vaccines and discussed the challenges and prospects of the vaccine-based approaches in a global crisis.Overall,most of the current vaccines have shown safety and efficacy/effectiveness during actual clinical trials or in the real-world studies,indicating a development of pandemic control.However,many challenges are faced by pandemic control in terms of maximizing the effect of vaccines,such as rapid vaccine coverage,strategies to address variants with immune escape capability,and surveillance of vaccine safety in the medium-and long-terms.

关键词： COVID-19 SARS-CoV-2 vaccine safety efficacy effectiveness immunogenicity

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Cell membrane-encapsulated nanoparticles for vaccines and immunotherapy

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Particuology 2022年第5期20卷 35-42页

作者： Wei Xiang Xue Liu Lili Zhang Chao Liu Gang Liu state key laboratory of molecular vaccinology and molecular diagnostics and Center for molecular Imaging and Translational Medicine School of Public Health.Xiamen UniversityXiamen 361102China state key laboratory of molecular vaccinology and molecular diagnostics and national institute of diagnostics and vaccine development in infectious disease School of Public HealthXiamen UniversityXiamen 361102China ShenZhen Research institute of Xiamen University.Shenzhen 518057 China

Functionalized nanoparticles are widely used in drug targeted delivery and immune microenvironment regulation.As a new type of biomaterial,cell-derived carriers are receiving considerable attention in clinical translation owing to their desirable biocompatibility and lower toxicity.Importantly,cell membrane-encapsulated nanoparticles can achieve specific biological effects from the benefit of their parent cell characteristics.In this review,we introduce the cell membrane coating technologies that are under extensive investigation,we also summarize various applications that have been developed for immunotherapy,and discuss the prospects in this field.With further understanding and integration with advanced biotechnology methods,it is believed that the continuing development of cell membrane-encapsulated nanoparticles will achieve promotion in clinical application.

关键词： Cell membrane Nanoparticle vaccine Immunotherapy

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

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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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A new track for antibacterial treatment:Progress and challenges of using cytomembrane-based vesicles to combat bacteria

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Particuology 2023年第7期78卷 136-146页

作者： Jiaxuan Xie Xuan Liu Gang Liu state key laboratory of molecular vaccinology and molecular diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen361102China Center for molecular Imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen361102China

The emergence and re-emergence of antibiotic-resistant bacteria,especially superbugs,are leading to complicated infections that are increasingly difficult to treat.Therefore,novel alternative antimicrobial therapies are urgently needed to reduce the morbidity and mortality caused by antibiotic resistance.The development of biomimetic-based therapy is expected to provide innovative means for addressing this challenging task.As a kind of novel biomaterial,cytomembrane-based vesicles(MVs)continue to receive considerable attention in antimicrobial therapy owing to their inherent biocompatibility,design flexi-bility,and remarkable ability to interact with biological molecules or the surrounding environment.These remarkable cell-like properties and their inherent interaction with pathogens,toxins,and the immune system underlie MVs-based functional protein therapy and targeted delivery to develop advanced therapeutic strategies against bacterial infection.This review provides a fundamental under-standing of the characteristics and physiological functions of cytomembrane-based vesicles,focusing on their potential to combat bacterial infections,including detoxification,immune modulation,antibiotics delivery,and physical therapy.In addition,the future possibilities and remaining challenges for clinically implementing MVs in the field of antibacterial treatment are discussed.

关键词： Cytomembrane-basedvesicles Bacterial resistance Antibacterial therapy Drug delivery

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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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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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development of functional antibodies against influenza B virus by activation-induced cytidine deaminase in hybridoma cells

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Virologica Sinica 2022年第4期37卷 619-622页

作者： Yuanzhi Chen Chenguang Shen Jing Chen Junyu Chen Fentian Chen Limin Zhang Xue Liu Siyuan Chen Sen Xue Yongliang Liu Jixian Tang Quan Yuan Yixin Chen Wenxin Luo Ningshao Xia national institute of diagnostics and vaccine development in infectious diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsSchool of Public Health&School of Life ScienceXiamen UniversityXiamen 361102China Biosafety Level-3 laboratory School of Public HealthSouthern Medical UniversityGuangzhou 510515China

Dear Editor,Influenza B viruses(IBVs)have circulated among humans for more than 80 years.Seasonal influenza virus epidemics caused by two IBV lines(Victoria and Yamagata)and influenza A virus have considerable effects on public health globally and result in approximately290,000–650,000 annual influenza-attributed deaths(Caini et al.,2015;Pan et al.,2015).Currently,the most effective countermeasures against influenza B virus infections are influenza virus vaccines(Subbarao and Matsuoka,2013).However,these vaccines have limited efficacy because only strain-matched humoral immune responses are induced.

关键词： influenza activation globally

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New discovery of high-affinity SARS-CoV-2 spike S2 protein binding peptide selected by PhIP-Seq

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Virologica Sinica 2022年第5期37卷 758-761页

作者： Mengyuan Chen Shuizhen He Hualong Xiong Dongxu Zhang Shaojuan Wang Wangheng Hou Xiaomei Zhu Jin Wang Yang Huang Congming Hong Yubin Wu Ruoyao Qi Tianying Zhang Quan Yuan Tingdong Li Yixin Chen Shiyin Zhang Shengxiang Ge Jun Zhang Ningshao Xia state key laboratory of molecular vaccinology and molecular diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Public HealthXiamen UniversitySouth Xiang'an RoadXiamen361102China Xiamen Haicang Hospital Haiyu RoadXiamen361026China School of Life Sciences Xiamen UniversitySouth Xiang'an RoadXiamen361102China

Dear Editor,Theworld had suffered pandemics of COVID-19 caused by SARS-CoV-2.At the time ofwriting,COVID-19 is still widely spreading inmany countries and regions,and by June 14,2022,totally 532,887,351 cases,including 6,307,021 deaths,were reported globally(WHO,https://covid19.***.int/table).Powerful measures,such as prophylactic and therapeutic interventions against the virus,are in urgent need for COVID-19 control and prevention.The spike protein,which is expressed on the virus surface,is the key determinant of viral-host interaction(Ng et al.,2021)and mediates the virus entry.

关键词： PhIP totally

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