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Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to ***,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD *** several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on *** this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different *** results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD ***,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological *** the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the ***,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild *** summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced *** models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

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Protectivity of Freeze Dried Inactivated Rift Valley Fever vaccine

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Open Journal of Veterinary Medicine 2024年第2期14卷 21-37页

作者： Diana M. Abulmagd Mohamed Hassan Atwa Noha Ezz Aldin Marwa Yehia Hammad Taradi Abdel Fattah Said Rift Valley Fever vaccine Research Department Veterinary Serum and Vaccine Research Institute Agriculture Research Center (ARC) Cairo Egypt

Background: Vaccinations for animals are crucial for food production, animal welfare, public health, and animal health. They are an affordable way to stop animal sickness, increase food production efficiency, and lessen or stop the spread of zoonotic diseases to humans. Animal vaccines that are both safe and efficacious are vital to modern culture. The vaccine should induce a strong, protective and prolonged immune response against the antigenic factor. In order to achieve these goals, novel vaccination techniques and an efficient adjuvant are required to render the vaccine immunogenically protective and trigger a strong immune response. Aim: Our study aims to promote and enhance the immunogenicity against RVF virus disease through lyophilized inactivated RVF vaccine through induction of early cellular, high and prolonged humeral immunity in vaccinated animals using cabopol as stabilizer and Saponin or normal saline as a diluent at time of vaccination. Moreover, manufacturing of these vaccines is easy to be done. Results: The gained results revealed that RVF freeze-dried vaccine with Carbopol that reconstituted using Saponin elicited better immune response than that reconstituted using normal saline (NaCl). The cell mediated immune response as represented by lymphocyte blastogenesis and phagocytic activity were markedly increased with high levels when we used Saponin as a diluent than that in group vaccinated with vaccine diluted with NaCl, on the other side the humeral immune response in group vaccinated using the Saponin as diluent is more detected and stayed within the protective level till the end of 11th month post vaccination (1.5 TCID50) while the immune response induced after using normal saline as a diluent stayed within the protective level till the end of 10th month post vaccination (1.8 TCID50). Conclusion: The use of Saponin as a diluent for reconstitution of the freeze dried RVF vaccine is preferable than the

关键词： Rift Valley Fever Saponin Cabopol Binary Ethylenemine Serum Neutralization Test

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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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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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Natural evidence of coronaviral 2′-O-methyltransferase activity affecting viral pathogenesis via improved substrate RNA binding

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2819-2834页

作者： Jikai Deng Shimin Yang Yingjian Li Xue Tan Jiejie Liu Yanying Yu Qiang Ding Chengpeng Fan Hongyun Wang Xianyin Chen Qianyun Liu Xiao Guo Feiyu Gong Li Zhou Yu Chen State Key Laboratory of Virology RNA InstituteCollege of Life Sciences and Frontier Science Center for Immunology and MetabolismWuhan UniversityWuhanChina School of Medicine Tsinghua UniversityBeijingChina School of Basic Medical Sciences Wuhan UniversityWuhanChina Animal Bio-Safety Level Ⅲ Laboratory/Institute for vaccine Research Wuhan University School of MedicineWuhanChina

Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune ***,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to ***,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic *** further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and *** residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA *** interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral ***,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence *** changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.

关键词： pathogenesis impaired alterations

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Even a Small Stride Can Have a Significant Impact:Enhancing the Effectiveness of Influenza vaccines

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Infectious Diseases & Immunity 2024年第2期4卷 56-57页

作者： Weixiao Wang Jingxin Li National vaccine Innovation Platform School of Public HealthNanjing Medical UniversityNanjing 210009China Jiangsu Provincial Medical Innovation center National Health Commission Key Laboratory of Enteric Pathogenic MicrobiologyJiangsu Provincial Center for Disease Control and PreventionNanjing 210009China.

Influenza viruses contribute substantially to respiratory diseases worldwide,including severe lower respiratory tract illnesses,hospitalization,and *** are approximately a billion cases of seasonal influenza worldwide annually,including 3 to 5 million cases of severe illness and 290,000 to 650,000 respiratory deaths.[1]Vaccination remains the best available intervention to prevent morbidity and mortality caused by influenza viruses circulating in humans,especially for older people with underlying health conditions,such as asthma,diabetes,and cardiovascular *** with influenza virus can cause the greatest morbidity and mortality effects.[2]However,the effectiveness of traditional standard-dose inactivated influenza vaccines is not satisfactory,with vaccine effectiveness ranging from 20%in years in which the vaccine is antigenically mismatched to the circulating viral strain[3]to 40%to 60%in years in which the vaccine is antigenically well matched.[4]

关键词： vaccine mortality annually

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Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

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Current Medical Science 2024年第1期44卷 121-133页

作者： Ting-ting WEI Wen XU Bo TU Wan-xue ZHANG Xin-xin YANG Yiguo ZHOU Shan-shan ZHANG Jun-lian YANG Ming-zhu XIE Juan DU Wei-wei CHEN Qing-bin LU Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Department of Infectious Disease The Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China Department of Laboratorial Science and Technology&vaccine Research center School of Public HealthPeking UniversityBeijing 100191China Department of Health Policy and Management School of Public HealthPeking UniversityBeijing 100191China Global center for Infectious Disease and Policy Research&Global Health and Infectious Diseases Group Peking UniversityBeijing 100191China Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijing 100191China

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains *** the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were *** In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had *** samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted *** Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and *** metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid *** sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI *** and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

关键词： human adenovirus metabonomic lipids pneumonia upper respiratory tract infection

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Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of Virology Chinese Academy of SciencesWuhanChina vaccine and Immunology Research center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

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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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Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China

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Infectious Diseases of Poverty 2024年第1期13卷 42-52页

作者： Jian Wang Li Qiu Shuang Bai Wei Zhao Ao Zhang Jing Li Jun-Nan Zhang Shan-Shan Zhou Ren Qiu Zhu Huang Jv-Xia Liu Ting-Bin Wang Xue Sun Jiang Wu Qun Zheng Bin He Min Lv Beijing center for Disease Prevention and Control BeijingChina Beijing Research center for Respiratory Infectious Diseases BeijingChina Hainan Provincial center for Disease Control and Prevention HaikouChina Haikou center for Disease Control and Prevention HaikouHainanChina Wanning center for Disease Control and Prevention WanningHainanChina Baisha County center for Disease Control and Prevention BaishaHainanChina Qiongzhong County center for Disease Control and Prevention QiongzhongHainanChina

Background The thirteen-valent pneumococcal conjugate vaccine(PCV13)is not included in the national immu-nization program and is administered voluntarily with informed consent in *** preparation for assessing the impact of pilot introduction in Hainan Province,we conducted a carriage study among children under 5 years of age from four locations in Hainan Province,*** From March to June 2022,nasopharyngeal(NP)swabs,collected from healthy children aged younger than 59 months who lived in the 4 different locations(Haikou,Wanning,Baisha and Qiongzhong)in Hainan Province,were tested for pneumococcus using conventional *** isolates were serotyped using the Quel-lung *** factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age,daycare attendance and other *** Pneumococcus was isolated in 710(30.4%)of the 2333 children *** 737 pneumococci,29 serotypes were identifed;60.9%were PCV13 serotypes;the most common vaccine serotypes were 6B(20.4%),19F(13.0%),6A(11.9%)and 23F(6.1%);and the most common nonvaccine serotypes were 23A(12.9%),34(6.1%)and nontypeable(NT)pneumococci(5.6%).Children vaccinated with PCV13 had lower carriage(17.7%vs 32.5%;P=0.0001)and fewer PCV13 serotypes(41.9%vs 62.7%;P=0.0017)compared to unimmunized *** adjustment,NP carriage Was higher among children attending daycare(aOR=2.3,95%CI:1.7-3.2),living in rural areas(aOR=1.4,95%CI:1.1-1.8),living with siblings(aOR=1.3,95%CI:1.0-1.6)and whose mothers had completed senior high/technical sec-ondary school(aOR=1.5,95%CI:1.1-2.0).In contrast,completion of 3-4 doses of PCV13 were associated with a lower carriage rate(aOR=0.6,95%CI:0.4-0.9).Conclusions We established the baseline of pneumococcal carriage,serotype distribution and PCV13 immuni-zation rates among healthy children under 5 years of age in Hainan Province,prior to the introduction of PCV13 into th

关键词： Pneumococcus Nasopharyngeal carriage Serotypes distribution Children Hainan Province China

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