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Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

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Signal Transduction and Targeted Therapy 2024年第1期9卷 47-50页

作者： Mengyu Guo Mingjing Cao Jiufeng Sun Ziwei Chen Xin Wang lianpan dai George F.Gao Yuliang Zhao Yaling Wang Chunying Chen CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijingChina Guangdong Provincial Institute of Public Health Guangdong Provincial Center for Disease Control and PreventionGuangzhouChina CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyBeijingChina

Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).

关键词： manganese immunity protective

3种平台Delta-Omicron嵌合RBD二聚体新型冠状病毒疫苗的免疫原性头对头比较

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科学通报 2024年第10期69卷 1351-1360页

作者：杨康吉徐坤张丽君韩雨旋周东明夏乾峰戴连攀高福海南医学院热带医学院热带转化医学教育部重点实验室海口571199 中国科学院北京生命科学研究院免疫与健康联合研究中心北京100101 中国科学院微生物研究所中国科学院病原微生物与免疫学重点实验室北京100101 天津医科大学基础医学院天津300070

新型冠状病毒(新冠病毒)在全球范围内流行,对公共卫生和人民生命健康造成了巨大威胁,新冠病毒疫苗的研发和使用对预防疾病和控制疫情起到了关键作用.基于包括重组蛋白亚单位、病毒载体、mRNA脂纳米颗粒在内的多种技术平台开发的疫苗都... 详细信息

新型冠状病毒(新冠病毒)在全球范围内流行,对公共卫生和人民生命健康造成了巨大威胁,新冠病毒疫苗的研发和使用对预防疾病和控制疫情起到了关键作用.基于包括重组蛋白亚单位、病毒载体、mRNA脂纳米颗粒在内的多种技术平台开发的疫苗都获得了使用.然而,由于抗原设计的差异、免疫剂量和注射间隔的差别,不同疫苗平台之间的免疫效果无法直接比较.因此,本研究以Delta-Omicron嵌合RBD二聚体为免疫原,对广泛使用的3个疫苗平台(重组蛋白亚单位疫苗、腺病毒载体疫苗和mRNA疫苗)进行了免疫原性头对头比较,通过小鼠模型比较了它们同源接种和序贯接种所诱导的体液免疫和细胞免疫反应的差异.结果显示,小鼠在免疫同源的两剂疫苗后,m RNA疫苗诱导的结合抗体和中和抗体滴度都最高,其次分别是重组蛋白亚单位疫苗和腺病毒载体疫苗;异源加强免疫的结果显示,不管是以重组蛋白亚单位疫苗、腺病毒载体疫苗或者mRNA疫苗初免,以mRNA疫苗作为第2针加强免疫均能诱导更强的体液免疫反应.此外,在疫苗激发的细胞免疫方面,mRNA疫苗诱导了较强的CD4^(+)T细胞反应,腺病毒载体疫苗诱导了较强的CD8^(+)T细胞反应,而亚单位疫苗刺激的细胞免疫反应以CD4^(+)T细胞为主,但在强度上较弱.本研究具有重要的应用价值,为未来新一代的新冠病毒疫苗研发和接种策略提供了指导.

关键词：新型冠状病毒亚单位疫苗腺病毒载体疫苗 m RNA疫苗抗体 T细胞

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Inside-out assembly of viral antigens for the enhanced vaccination

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3144-3157页

作者： Fengqiang Cao Sha Peng Yaling An Kun Xu Tianyi Zheng lianpan dai Kenji Ogino To Ngai Yufei Xia Guanghui Ma State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190PR China Graduate School of Bio-Applications and Systems Engineering Tokyo University of Agriculture and Technology2-24-16 NakachoKoganeiTokyo184-8588Japan Institute of Global Innovation Research Tokyo University of Agriculture and Technology2-24-16 NakachoKoganei-shiTokyo184-8588Japan CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101PR China Savaid Medical School University of Chinese Academy of SciencesBeijingPR China Key Laboratory of Tropical Translational Medicine of Ministry of Education School of Tropical Medicine and Laboratory MedicineThe First Affiliated HospitalHainan Medical UniversityHainan571199PR China Zhejiang University School of Medicine Hangzhou310058PR China Department of Chemistry The Chinese University of Hong KongShatinN.T.Hong Kong999077PR China University of Chinese Academy of Sciences Beijing100049PR China Innovation Academy for Green Manufacture Chinese Academy of Sciences Beijing100190PR China

Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens,but neglect that pathogens evolve to evade the immune system rather than to provoke *** the case of enveloped RNA viruses,it is the natural dissemination of nucleocapsid protein(NP,core antigen)and surface antigen that delays NP exposure to immune ***,we report a multi-layered aluminum hydroxide-stabilized emulsion(MASE)to dictate the delivery sequence of the *** this manner,the receptor-binding domain(RBD,surface antigen)of the spike protein was trapped inside the nanocavity,while NP was absorbed on the outside of the droplets,enabling the burst release of NP before *** with the natural packaging strategy,the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance,which subsequently boosted CD40+DC activations and the engagement of the lymph *** both H1N1 influenza and SARS-CoV-2 vaccines,rMASE significantly increased antigen-specific antibody secretion,memory T cell engagement,and Th1-biased immune response,which diminished viral loads after lethal *** simply reversing the delivery sequence of the surface antigen and core antigen,the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

关键词： vaccination outside evolve

Avian influenza A(H7N9)virus:from low pathogenic to highly pathogenic

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Frontiers of Medicine 2021年第4期15卷 507-527页

作者： William J.Liu Haixia Xiao lianpan dai Di Liu Jianjun Chen Xiaopeng Qi Yuhai Bi Yi Shi George F.Gao Yingxia Liu Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Third People’s HospitalShenzhen518114China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing102206China Laboratory of Protein Engineering and Vaccines Tianjin Institute of Industrial BiotechnologyChinese Academy of Sciences(CAS)Tianjin300308China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS Key Laboratory of Special Pathogens and Biosafety Chinese Academy of SciencesWuhan430071China National Virus Resource Center Chinese Academy of SciencesWuhan430071China University of Chinese Academy Sciences Beijing100049China Center for Influenza Research and Early Warning Chinese Academy of SciencesBeijing100101China Chinese Center for Disease Control and Prevention Beijing102206China

OriginalTranslation The avian influenza A(H7N9)virus is a zoonotic virus that is closely associated with live poultry *** has caused infections in humans in China since *** waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017.H7N9 with low-pathogenicity dominated in the first four waves,whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave,causing wide *** and officials from China and other countries responded quickly,controlled the epidemic well thus far,and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness ***,we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the *** was summarized and discussed from the perspectives of molecular epidemiology,clinical features,virulence and pathogenesis,receptor binding,T-cell responses,monoclonal antibody development,vaccine development,and disease *** data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses,such as SARS-CoV-2.

关键词： H7N9 HPAIV clinical features epidemiology hemagglutinin immunity pathogenesis vaccine

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Vaccine and protective antibody: the development of interventions against Zika virus

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Vaccine and protective antibody: the development of interven...

Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody

第十三届全国免疫学学术大会

作者： lianpan dai Kun Xu Jian Song Fu Gao Beijing Institutes of Life Science Chinese Academy of Sciences Institute of Microbiology Chinese Academy of Sciences

The Zika virus(ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. ZIKV disease has spilled over into 84 countries and regions. So far, no prophylactics and therapeutics are available, therefore, countermeasure development is urgently demanded. Envelope protein mediated flavivirus adsorption and entry into host cells. therefore, it represents the major target for neutralizing antibodies and protective immunogen. We determined the crystal structure of envelope(E) protein of ZIKV, showing a typical type II viral fusion glycoprotein. Since the fusion loop(FL) of E protein is highly conserved among flaviviruses, we choose a FL-targeting broadly neutralizing antibody 2 A10 G6 for evaluation. 2 A10 G6 can partially protect lethal challenge of ZIKV infection. By analysis the structure of E in complexed with 2 A10 G6, we dissected the classic binding mode of FL-targeting *** chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low pre-existing immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7(AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E is sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed high neutralizing antibody titers within one week post-vaccination and the elicited antisera can cross-neutralize heterologous ZIKV strains. Impressively, one-dose inoculation of AdC7-M/E conferred mice sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against the ZIKV-induced testicular damage in mice model. These data demonstrate that AdC7-M/E is

关键词： Zika virus protective antibody antibody epitope Viral vector vaccine Zika vaccine

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Structures of the Zika Virus Envelope Protein and Its Comple...

A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites IV and V of the viral fusion glycoprotein

第十一届全国免疫学学术大会

作者： dai lianpan Song Jian Lu Xishan Shi Yi Qi Jianxun Gao Fu Research Network of Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of Sciences CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences

Zika virus(ZIKV),a mosquito-borne flavivirus,has caused an urgent global health concern as microcephaly and serious neurological complications are associated with ZIKV *** envelope(E)glycoprotein is responsible for virus entry and represents the major target of neutralizing ***,we report the crystal structure of ZIKV E protein at 2.0 and its complex with a flavivirus broadly neutralizing antibody 2A10G6 at 3.0?.By structural

关键词： Flavivirus Zika virus Antibody Protection Neutralization

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hLife 2023年第1期1卷 12-25页

作者： lianpan dai Jian Song Lili Xu Zhao Gao Senyu Xu Yan Chai Liang Wang Mi Yang Tong Ma Qihui Wang Sushan Cao Junming Yie Gang Zou Zhengde Xie Jim Zhen Wu George Fu Gao CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina Key Laboratory of Major Diseases in Children Ministry of EducationNational Clinical Research Center for Respiratory DiseasesBeijing Key Laboratory of Pediatric Respiratory Infection DiseasesResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016Laboratory of Infection and VirologyBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Shanghai Ark Biopharmaceutical Co. Ltd.ShanghaiChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina

Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the *** immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in *** we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as *** mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in *** RV11 escape mutant was identified,which contains an S443P mutation in F *** structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F ***11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.

关键词： Respiratory syncytial virus(RSV)antibody RSV monoclonal antibody RSV fusion glycoprotein RSV epitope palivizumab RSV prophylaxis

Near-field wideband beam training for ELAA with uniform circular array

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Science China(Information Sciences) 2024年第6期67卷 370-383页

作者： Yuhao CHEN Linglong dai Department of Electronic Engineering Tsinghua UniversityBeijing National Research Center for Information Science and Technology (BNRist)

Extremely large-scale antenna array(ELAA) at millimeter wave(mmWave) and Terahertz(THz)band has been considered a key technology for combating high attenuation in high-frequency bands in future6G communications. Uniform circular arrays(UCAs) have attracted much attention because of their ability to provide flat beamforming gain at all angles. To realize efficient beamforming, beam training is widely used to acquire channel state information. However, with a large antenna number, the beam training overhead in ELAA systems becomes overwhelming. Moreover, with a large bandwidth, the beam defocus effect severely degrades beam training accuracy. To address these issues, this paper proposes a frequency-dependent focusing(FDF)-based beam training scheme to realize effective beam training in near-field wideband ELAA systems with UCA. Specifically, we first analyze the FDF property of UCA, where signals at different subcarriers can simultaneously focus on different distances. Then, by exploiting the FDF property to search different distances using different subcarriers simultaneously, we design a hierarchical codebook and propose an FDFbased beam training scheme. To reveal the effectiveness of the proposed scheme, we compare its necessary beam training overhead with that of existing schemes. Finally, the simulation results demonstrate that the proposed scheme can achieve accurate beam training in near-field wideband UCA systems with a low beam training overhead.

关键词： extremely large-scale antenna array (ELAA) uniform circular array (UCA) near-field wideband beam training

Seismic performance evaluation of water supply pipes installed in a full-scale RC frame structure based on a shaking table test

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Earthquake Engineering and Engineering Vibration 2024年第1期23卷 163-178页

作者： Wu Houli Guo Endong Wang Jingyi dai Xin dai Chenxi Key Laboratory of Earthquake Engineering and Engineering Vibration Institute of Engineering MechanicsChina Earthquake AdministrationHarbin 150080China Key Laboratory of Earthquake Disaster Mitigation Ministry of Emergency ManagementHarbin 150080China

As an important part of nonstructural components,the seismic response of indoor water supply pipes deserves much *** paper presents shaking table test research on water supply pipes installed in a full-scale reinforced concrete(RC)frame *** material pipes and different methods for penetrating the reinforced concrete floors are combined to evaluate the difference in seismic *** response spectra and pipe acceleration amplification factors based on test data are discussed and compared with code provisions.A seismic fragility study of displacement demand is conducted based on numerical *** acceleration response and displacement response of different combinations are *** results show that the combination of different pipe materials and different passing-through methods can cause obvious differences in the seismic response of indoor riser pipes.

关键词： water supply pipe different materials shaking table test amplification factor seismic fragility

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