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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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Crystal structures of RNA-dependent RNA polymerases from Jingmen tick virus and Alongshan virus

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hLife 2024年第1期2卷 18-31页

作者： Zhenyang Liu Qi Peng Pu Han Lu Kuai Jianxun Qi Yi Shi CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina Beijing Life Science Academy BeijingChina International Institute of vaccine research and Innovation Savaid Medical SchoolUniversity of Chinese Academy of SciencesBeijingChina center for Influenza research and Early-warning CAS-TWAS Center of Excellence for Emerging Infectious DiseaseChinese Academy of SciencesBeijingChina research Unit of Adaptive Evolution and Control of Emerging Viruses Chinese Academy of Medical SciencesBeijingChina

Jingmenviruses are a group of flavi-like viruses with segmented genome and have been found in various types of hosts,including humans,cattle,monkeys,bats,rodents,sheep,ticks,mosquitoes and ***,including the Jingmen tick virus(JMTV)and Alongshan virus(ALSV),have been associated with febrile illness and flu-like symptoms in *** polymerase plays critical roles in genome replication and transcription and is an ideal target for antiviral ***,we determined the crystal structures of RNA-dependent RNA polymerase(RdRp)domains of JMTV and ALSV at 2.6Åand 3.2Åresolutions,*** overall structures of JMTV and ALSV RdRp domains are similar to those from the typical unsegmented viruses in Flaviviridae family,especially the Flavivirus *** and ALSV RdRps can be divided into three subdomains and the catalytical Motif A-G are conserved like the typical flaviviruses,whereas the zinc-binding pockets are absent from the JMTV and ALSV *** 50-ends of jingmenvirus genomes are varied in length and sequence,and a highly conserved 8-nucleotide element located on the tip of stem loop A was identified and shown to be required for binding with RdRp and performing de novo replication *** findings provide important structural insights into RdRp of segmented flavivirus and reveal the key region of virus genome responsible for replication initiation,which would promote molecular understanding of segmented flavivirus replication and the structure-based design of antiviral drugs against flaviviruses.

关键词： Jingmenviruses X-rays RNA-dependent RNA polymerase replication

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The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner

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Cancer Communications 2024年第2期44卷 273-277页

作者： Mi-Jeong Kim Ji Young Kim Ji Hye Shin Juhee Son Yeeun Kang Soo-Kyung Jeong Duk-Hwan Kim Kyun-Hwan Kim Eunyoung Chun Ki-Young Lee Department of Immunology Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSuwonRepublic of Korea research and Development center CHA Vaccine InstituteSeongnam-siRepublic of Korea Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&TechnologySamsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea

Dear editor,Severe acute respiratory syndrome coronavirus2(SARS-CoV-2)infection can lead to severe outcomes in patients with cancer[1].It has been reported that patients with lung cancers disproportionately manifest severe COVID-19 with a high rate of hospitalization and death[2].Notably,the SARS-CoV-2 Spike(S)protein can induce hyper-inflammation in both epithelial cells and macrophages through toll-like receptor(TLR)1/TLR2 or TLR2/6-dependent nuclear factor-kappaB(NF-κB)path-way[3].However,molecular and cellular evidence on whether the SARS-CoV-2 virus affects the severity of lung cancer patients through TLR1/2 or TLR2/6 signaling remains unclear.

关键词： lung TLR2 invasion

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Mechanism of Mingjing Granules in Treating Wet Age-Related Macular Degeneration Based on Network Pharmacology and Experimental Verification

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 22-32页

作者： Xiao-Yu Li Li-Na Liang Wei-Jun Zhang Yun Gao Qiang Chen Eye Function Laboratory Eye HospitalChina Academy of Chinese Medical SciencesBeijingChina China Evidence-Based Medicine center for Traditional Chinese Medicine BeijingChina center for East-West Medicine UCLA David Geffen School of MedicineLos AngelesCAUSA

Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and to provide a new reference for the currently limited treatment of *** and Methods:We searched TCMSP,GeneCards,OMIM,PharmGkb,TTD,and DrugBank database to screen the main active ingredients of Mingjing granules and their therapeutic targets of *** network of active components and targets was constructed using Cytoscape3.6.1 software,which was also used for the topological analysis of target *** network of Protein-Protein Interactions(PPI)was mapped using the String *** also used R language to do the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway for additional *** docking studies were finished by Chemoffice,Autodock,and ***,the efficacy of the Mingjing granules was examined in animal experiments,in which we used enzyme-linked immunosorbent assay to the contents of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9)levels in peripheral ***:Active compounds,including quercetin,lignocaine,and kaempferol,were *** network analysis showed that tumor necrosis factor(TNF),MMP-9,epidermal growth factor(EGF),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase-3(CASP3)were related to both Mingjing granules and *** and KEGG pathway analysis showed that these targets were mainly involving lipids and atherosclerosis,TNF,and interleukin-17(IL-17)signaling *** studies suggested that quercetin and luteolin can fit in the binding pocket of four target proteins(CASP3,EGF,PTGS2,and TNF).In the vivo experiment,the Mingjing granules were found to be effective on the expression of VEGF and MMP-9 in peripheral ***:This study initially reveals the multi-constituent,multi-target,and multi-pathway mechanism of action of Ming

关键词： Experimental verification Mingjing granules molecular docking network pharmacology wet age-related macular degeneration

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3'-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat die

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Food Science and Human Wellness 2024年

作者： Wei Zhang Meizhen Zhu Kelsang Dekyi Linxi Zheng Yichen Zhang Youping Lv Dongbei Guo Xiaoxuan Chen Lili Pan Xinyue Wang Hongwei Li State Key Laboratory of vaccines for Infectious Diseases， Xiang An Biomedicine Laboratory， School of Public Health， Xiamen University State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics，National Innovation Platform for Industry-Education Integration in vaccine research， Xiamen University Department of Nutrition， Zhongshan Hospital (Xiamen)， Fudan University Xiamen Clinical research center for Cancer Therapy

Recent research has indicated that sialic acid， such as free sialic acid (N-acetylneuraminic acid， Neu5Ac) and bound sialic acid (3'-sialyllactose， 3'-SL)， can ameliorate disorders associated with glycolipid metabolism， although the underlying mechanisms have yet to be determined. We examined the effects of 3'-SL on glycolipid metabolism in mice fed a high-fat diet. Male C57BL/6J mice were divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac， and low-，moderate-， and high-dose 3'-SL]. After 8 weeks of continuous gavage intervention， mice in the 3'-SL intervention groups had lower body weight and total fat content; reduced fasting blood glucose， triglycerides， low-density lipoproteins and oxidized-low-density lipoproteins; and increased high-density lipoproteins，but no dosage-dependent of 3'-SL intervention was found， 3’-SL＿M intervention as optimal for further exploration. 3'-SL intervention could increase respiratory exchange ratio， energy expenditure， and amount of exercise performed. 3'-SL increased the colonic abundances of Akkermansia， Lactobacillus， and Bacteroides， and reduced those of Erysipelatoclostridium， Faecalibaculum， and Aldercreutzia. Changes were also observed in colonic metabolites， and liver gene transcript and metabolites， which were mainly enriched in bile secretion， taurine and hypotaurine metabolism， and insulin resistance. Additionally， 3'-SL was observed to regulate genes associated with physiological rhythms， including clock， per2， cry1， and bhihe41. Collectively， our findings indicate that 3'-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets. Compared with Neu5Ac， 3'-SL intervention can ameliorate intestinal flora disorders， enhance bile acid circulation， increase tissue energy expenditure， and reduce lipid synthesis， thereby promoting lipid-lowering effects mediated via the liver–gut axis， and can a

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Supercritical fluid technology:A game-changer for biomacromolecular nanomedicine preparation and biomedical application

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Chinese Chemical Letters 2024年第7期35卷 89-99页

作者： Yating Zheng Yulan Huang Jing Luo Xuqi Peng Xiran Gui Gang Liu Yang Zhang State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryNational Innovation Platform for Industry-Education Integration in Vaccine ResearchState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Shen Zhen research Institute of Xiamen University Shenzhen 518057China Division of Urology and Department of Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components,good biocompatibility,and high ***,their large relative molecular weight,complex structure,susceptibility to degradation,and poor stability limit their *** can address these issues by improving the therapeutic value,bioavailability,permeability,and absorption of biomacromolecules while regulating their retention time in the ***,compelling evidence has been reported that supercritical fluid(SCF)technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental *** this review,we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine,and extensively discuss their characteristics and *** particular,the protein-based,nucleic acid-based,and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized,and the potential for industrial production of biomacromolecular drugs is also *** further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.

关键词： Biomacromolecules Supercritical fluid technology Therapeutic proteins Gene therapy Nanomedicine

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COVID-19 vaccines and beyond

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Cellular & Molecular Immunology 2024年第3期21卷 207-209页

作者： Yiyuan Liu Danying Li Jiahuai Han State Key Laboratory of Cellular Stress Biology Innovation Center for Cell BiologySchool of Life SciencesXiamen UniversityXiamenFujianChina Laboratory Animal center Xiamen UniversityXiamenFujianChina research Unit of Cellular Stress of CAMS Cancer Research Center of Xiamen UniversityXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenFujianChina

Hundreds of vaccines have been developed worldwide for Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the cause of Coronavirus disease 2019(COVID-19),since the beginning of the *** vaccines have saved innumerable lives and contributed to partial control of the COVID-19 *** of the vaccines approved for clinical use exhibit satisfactory initial protection rates against corresponding ***,vaccine protection declines over time,with almost all vaccines falling below 50%protection after 6 months[1].In the case of natural infections,protection lasts longer,but the incidence of reinfection is also quite high.

关键词： vaccines acute beyond

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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 *** immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization ***,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly *** this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and *** 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 *** 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 *** Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to *** swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI ***,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 *** 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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Comparison of 1 Versus 2 Doses of Quadrivalent Influenza vaccine in 3-8-Year-Old Children with Different Immunological States—Jiangsu Province,China,2021

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China CDC weekly 2024年第19期6卷 424-430,I0002-I0004页

作者： Qian Liu Pengfei Jin Jingxin Li Xiaoqin Chen Chenhao Wang Qingbin Lu Wei Jiang Shixuan Zhang Lairun Jin Hongxin Pan Xue Guo Fengcai Zhu School of Public Health Southeast UniversityNanjing CityJiangsu ProvinceChina Jiangsu Provincial Medical Innovation center National Health Commission Key Laboratory of Enteric Pathogenic MicrobiologyJiangsu Provincial Center for Disease Control and PreventionNanjing CityJiangsu ProvinceChina Donghai County center for Disease Control and Prevention Donghai CityJiangsu ProvinceChina Changchun Institute of Biological Products Co. Ltd.Changchun CityJilin ProvinceChina Department of Laboratorial Science and Technology&vaccine research center School of Public HealthPeking UniversityBeijingChina Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijingChina

Summary What is already known about this topic?The quadrivalent influenza vaccine(QIV)provides protection against a broader range of influenza strains by including strains of influenza A/H1N1,A/H3N2,B/Yamagata,and B/*** is added by this report?This study aimed to assess the immunogenicity and safety of administering a single dose compared to two doses of QIV in children,taking into consideration their previous influenza vaccination history.

关键词： ent doses Jiangsu

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Eliciting CD4-mimicking broadly neutralizing antibodies:new avenues towards the rational design of an HIV vaccine

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Signal Transduction and Targeted Therapy 2024年第3期9卷 836-838页

作者： Frauke Muecksch Oliver T.Fackler Department of Infectious Diseases Heidelberg UniversityMedical Faculty HeidelbergVirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany Chica and Heinz Schaller(CHS)research Group Department of Infectious DiseasesVirologyUniversity Hospital HeidelbergHeidelbergGermany Department of Infectious Diseases Heidelberg UniversityMedical Faculty HeidelbergIntegrative VirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany German Centre for Infection research(DZIF) Partner Site HeidelbergHeidelbergGermany

In a study recently published in Cell,Saunders et *** that a new anti-HIV vaccine triggers antibody responses resembling CD4-binding site broadly neutralizing antibody precursors in rhesus macaques.1 This study provid... 详细信息

关键词： al. vaccine rational

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