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Genomic surveillance of emerging SARS-CoV-2 Omicron variations in tianjin Municipality, China 2022

Biosafety and Health 2024年第2期6卷 61-69页

作者： Xin Gao Ming Zou Yue Lei Zhaolin Tan Zhichao Zhuang Baolu Zheng Aiping Yu Yanzhen Han Xiaohui Lu Xiaochang Liu Ying Wang Yuan Wang Liru Guo Guangwen Liu Wen Li Yang Liu Likun Lv Peiyong Ning Xiaoyan Li tianjin Centers for disease Control and Prevention Tianjin 300011China tianjin key laboratory of pathogenic microbiologyof infectious disease Tianjn Centers for Disease Controland PreventionTianjin 300011China

The coronavirus disease 2019(COvID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has severely impacted public health.In 2022,the Omicron variant of SARS-CoV-2 rapidly became the dominant circulating variant in the local COVID-19 outbreaks in tianjin Municipality,China.To gain a deeper understanding of the genetic variations of the Omicron variant in tianjin,specimens from indi-viduals who tested positive for SARS-CoV-2 between December 2021 and November 2022 were used for virus whole genome sequencing and phylogenetic analysis.A total of 1,674 high-quality Omicron sequences were obtained,consisting of 1,339 sequences from local cases belonging to 20 Phylogenetic Assignment of Named Global Outbreak(PANGO)lineages and 335 sequences from imported cases belonging to 70 lineages.tianjin experienced five waves of local outbreaks,accompanied by multiple substitutions among subvariants,ranging from the initial BA.1.1 lineage to the subsequent BA.2,BF.7,and BA.5.2 lineages.The evolutionary rate of local strains,estimated to be 28.999 substitutions per year,and the evolutionary rate of imported strains,estimated to be 24.946 substitutions per year,were lower than that of the strains circulating globally.The addi-tional substitutions and deletions of local strains have been used to identify and disrupt the virus transmission chains.The subvariants such as BA.5.2.48,BA.5.2.49,BF.7.14,and XBB.1 circulating in the fifth epidemic wave presented criterial immune escape mutations including S:R346T,S:L452R and S:F486V.It is essential to implement genomic surveillance strategies to investigate further the development of genomic mutation char-acteristics in the SARS-CoV-2 variant.This ongoing monitoring will contribute to a better understanding of the virus's genetic changes and aid in effective control measures.

关键词： Severeacute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirusdisease2019(COVID-19) Omicron variant Wholegenome sequencing(WGS)

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Characterization of whole genomes from recently emerging Mpox cases in several regions of China,2023

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Science China(Life Sciences) 2024年第5期67卷 1079-1081页

作者： Changcheng Wu Lunbiao Cui Yang Pan Ziquan Lv Mingxiao Yao Wenling Wang Fei Ye Weibang Huo Li Zhao Baoying Huang Fengcai Zhu Roujian Lu Yao Deng Quanyi Wang Wenjie Tan NHC key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China NHC key laboratory of Enteric pathogenic microbiology Jiangsu Provincial Medical Key Laboratory of Pathogenic Microbiology in Emerging Major Infectious DiseasesJiangsu Provincial Center for Disease Control and PreventionNanjing 210009China Beijing Center for disease Prevention and Control Beijing 100013China Central laboratory Shenzhen Center for Disease Control and PreventionShenzhen 518055China Shandong Center for disease Control and Prevention Jinan 250014China

Dear Editor,Mpox(formerly known as monkeypox)is a zoonotic disease caused by infection with the monkeypox virus(MPXV).Mpox cases have been sporadic over the past few decades,with outbreaks occurring in only a limited ... 详细信息

关键词： cases primarily imported

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Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

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Protein & Cell 2024年第6期15卷 403-418页

作者： Song Xue Yuru Han Fan Wu Qiao Wang key laboratory of Medical Molecular Virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles.Point mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)recognition.Here,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion.Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity.However,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major variants.The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions.Together,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关键词： ACE2 affinity maintained

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Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases

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Science China Life Sciences 2024年

作者： Ziqian Xu Lianpan Dai Jun Liu National key laboratory of Intelligent Tracking and Forecasting for infectious diseases (NITFID) National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention CAS key laboratory of Pathogen microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences

Vector-borne viruses, transmitted among humans and animal hosts through bites of vectors such as mosquitoes and ticks,pose a great and ongoing threat to public health and biosafety (Yang et al., 2022).Among them, dengue virus-induced epidemics, have dramatically increased worldwide in recent decades. The report released by the World Health Organization (WHO) at the end of 2023 showed that dengue epidemic globally surged in2023, with the number of reported cases nearing a historical peak.

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Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function

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National Science Review 2024年第2期11卷 145-154页

作者： Farong Ye Cheng Li Feng-Liang Liu Xinliang Liu Peng Xu Rong-Hua Luo Wenping Song Yong-Tang Zheng Tianlei Ying Biao Yu Ping Wang Center for Chemical Glycobiology Frontiers Science Center for Transformative Molecules Zhangjiang Institute for Advanced Study School of Chemistry and Chemical Engineering Shanghai Jiao Tong University MOE/NHC/CAMS key laboratory of Medical Molecular Virology Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection Shanghai Institute of Infectious Disease and BiosecurityShanghai Engineering Research Center for Synthetic ImmunologySchool of Basic Medical Sciences Shanghai Medical College Fudan University key laboratory of Animal Models and Human disease Mechanisms of Chinese Academy of Sciences/key laboratory of Bioactive Peptides of Yunnan Province Center for Biosafety Mega-Science Kunming Institute of ZoologyChinese Academy of Sciences State key laboratory of Bioorganic and Natural Products Chemistry Center for Excellence in Molecular Synthesis Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shenzhen Research Institute of Shanghai Jiao Tong University

Vaccines have been the primary remedy in the global fight against coronavirus disease 2019（COVID-19）.The receptor-binding domain（RBD） of the spike protein, a critical viral immunogen, is affected by the heterogeneity of its glycan structures and relatively low immunogenicity. Here, we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD, facilitating the elucidation of carbohydrate structure–function relationships. Five homogeneously glycosylated RBDs bearing biantennary glycans were prepared, three of which were conjugated to T-helper epitope(Tpep) from tetanus toxoid to improve their weak immune response. Relative to natural HEK293-derived RBD, synthetic RBDs with biantennary N-glycan elicited a higher level of neutralising antibodies against SARS-CoV-2 in mice. Furthermore, RBDs containing Tpepelicited significant immune responses in transgenic mice expressing human angiotensin-converting enzyme 2. Our collective data suggest that trimming the N-glycans and Tpepconjugation of RBD could potentially serve as an effective strategy for developing subunit vaccines providing efficient protection.

关键词： peptide ligation glycosylation glycoprotein

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Preparation and immunoprotective effects of a virus-like particle candidate vaccine of the dominant epidemic D3 genotype coxsackievirus A6 in China

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Biosafety and Health 2024年第1期6卷 28-34页

作者： Xiaoliang Li Xizhu Xu Jichen Li Huanhuan Lu Congcong Wang Rui Wang Jinbo Xiao Ying Liu Yang Song Jingdong Song Qiang Sun Yong Zhang Department of Public Health and Health Administration Shandong First Medical UniversityJinan 250117China National key laboratory of Intelligent Tracking and Forecasting for infectious diseases(NITFID) National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Polio laboratory WHO WPRO Regional Polio Reference LaboratoryNational Health Commission Key Laboratory for BiosafetyNational Health Commission Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102206China Department of Medical microbiology Weifang Medical UniversityWeifang 261053China

Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent HFMD.This study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs.The neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune pathways.The immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)mice.Immunological protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice models.Serum‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐YN2015.Furthermore,these levels were significantly higher with abdominal injection than intramuscular injection.The immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,respectively.For ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to survive.Overall,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.

关键词： Coxsackievirus A6 D3 genotype Virus‐like particle Immunoprotective effect

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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

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Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 115-127页

作者： Yang Yi Wenzhe Li Kefang Liu Heng Xue Rong Yu Meng Zhang Yang-Oujie Bao Xinyuan Lai Jingjing Fan Yuxi Huang Jing Wang Xiaomeng Shi Junhua Li Hongping Wei Kuanhui Xiang Linjie Li Rong Zhang Xin Zhao Xue Qiao Hang Yang Min Ye State key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing100191China Yunnan Baiyao International Medical Research Center Peking UniversityBeijing100191China CAS key laboratory of Pathogen microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS key laboratory of Special Pathogens and Biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Department of microbiology and infectious disease Center School of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing100191China Hubei Jiangxia laboratory Wuhan430000China Shenzhen Children's Hospital ShenzhenGuangdong518036China

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

关键词： COVID-19 Inflammation Licorice-saponin A3 Receptor-binding domain(RBD) SARS-CoV-2

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Species-level Microbiota of Biting Midges and Ticks from Poyang Lake

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Biomedical and Environmental Sciences 2024年第3期37卷 266-277,I0001-I0003页

作者： GONG Jian WANG Fei Fei LIU Yang Qing PU Ji DONG Ling Zhi ZHANG Si Hui HUANG Zhen Zhou HUANG Yu Yuan LI Ya Ben YANG Cai Xin TAO Yuan Meihui ZHAO Li Jun JIN Dong LIU Li Yun YANG Jing LU Shan Department of Epidemiology School of Public HealthShanxi Medical UniversityTaiyuan 030001ShanxiChina National key laboratory of Intelligent Tracking and Forecasting for infectious diseases National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Jiangxi Provincial key laboratory of Animal-Origin and Vector-Borne diseases Nanchang Center for Disease Control and PreventionNanchang 330038JiangxiChina Research Units of Discovery of Unknown Bacteria and Function Chinese Academy of Medical SciencesBeijing 100730China

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control.Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake.Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors.Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which m

关键词： Biting midge Tick Microbiota Pantoea Coxiella

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Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing

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Biomedical and Environmental Sciences 2024年第3期37卷 294-302页

作者： ZHANG Ya Li SU Wen Zhe WANG Rui Chen LI Yan ZHANG Jun Feng LIU Sheng Hui HU Dan He XU Chong Xiao YIN Jia Yu YIN Qi Kai HE Ying LI Fan FU Shi Hong NIE Kai LIANG Guo Dong TAO Yong XU Song Tao MA Chao Feng WANG Huan Yu Shaanxi University of Chinese Medicine Xianyang 712000ShaanxiChina National key laboratory of Intelligent Tracking and Forecasting for infectious diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Guangzhou Center for disease Control and Prevention Guangzhou 510000GuangdongChina Shandong Center for disease Control and Prevention Jinan 250000ShandongChina Department of Ophthalmology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Xi'an Center for disease Control and Prevention Xi’an 710054ShaanxiChina

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing.Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing.Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing.Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

关键词： Viral encephalitis Amplicon sequencing High-throughput sequencing Multipathogen detection

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