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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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Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

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Zoological Research 2024年第3期45卷 551-566页

作者： Chen Ling Su-Su Liu Yu-Ya Wang Gui-Tao Huo Yan-Wei Yang Nan Xu Hong Wang Yong Wu Yu-Fa Miao Rui Fu Yu-Wei Zhao Chang-Fa Fan College of Life Sciences Northwest UniversityProvincial Key Laboratory of Biotechnology of Shaanxi ProvinceXi’anShaanxi 710069China Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China national Center for Safety evaluation of Drugs National Institutes for Food and Drug Control(NIFDC)Beijing 100176China Division of HIV/AIDS and Sexually Transmitted Virus vaccines Institute for Biological Products ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China Division of laboratory Animal monitoring Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic *** etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and ***,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic ***,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle *** symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in ***-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene *** murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the *** on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to ***,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

关键词： HRAS THBS1 HCC driver factor NASH Fibrosis Cirrhosis HCC Treatment evaluation

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Immunogenicity and protective efficacy of a recombinant protein subunit vaccine and an inactivated vaccine against SARS-CoV-2 variants in non-human primates

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1170-1180页

作者： Qian He Qunying Mao Xiaozhong Peng Zhanlong He Shuaiyao Lu Jialu Zhang Fan Gao Lianlian Bian Chaoqiang An Wenhai Yu Fengmei Yang Yanan Zhou Yun Yang Yanyan Li Yadi Yuan Xujia Yan Jinghuan Yang Xing Wu Weijin Huang Changgui Li Junzhi Wang Zhenglun Liang Miao Xu Division of Hepatitis and Enterovirus vaccines Institute of Biological ProductsNational Institutes for Food and Drug ControlNHC Key Laboratory of Research on Quality and Standardization of Biotech ProductsNMPA Key Laboratory for Quality Research and Evaluation of Biological ProductsBeijing 102629People’s Republic of China Institute of medical Biology Chinese Academy of Medicine Sciences&Peking Union Medical CollegeKunming 650118People’s Republic of China

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the *** investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain(RBD)(PS-RBD)and whole inactivated virus particle vaccine(IV)against the variant strains,in this study,rhesus macaques were immunized with PS-RBD or IV vaccine,followed by a Beta variant(B.1.351)*** neutralizing activity against the Beta variant was reduced compared with that against the prototype,the decreased viral load in both upper and lower respiratory tracts,milder pathological changes,and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque ***,PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha,Beta,Delta,and Omicron variants in our study,though the neutralizing antibody(NAb)titers declined by varying degrees,demonstrating potential protection of PS-RBD against current circulating variants of concern(VOCs).Interestingly,although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant,it still showed reduction for viral load and significantly alleviated pathological *** correlates of vaccine-induced protection(CoP)like antibody-dependent cellular cytotoxicity(ADCC)and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.

关键词： protective vaccine neutral

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Non-small cell lung cancers(NSCLCs)oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5069-5084页

作者： Bopei Cui Lifang Song Qian Wang Kelei Li Qian He Xing Wu Fan Gao Mingchen Liu Chaoqiang An Qiushuang Gao Chaoying Hu Xiaotian Hao Fangyu Dong Jiuyue Zhou Dong Liu Ziyang Song Xujia Yan Jialu Zhang Yu Bai Qunying Mao Xiaoming Yang Zhenglun Liang Division of Hepatitis and Enterovirus vaccines NHC Key Laboratory of Research on Quality and Standardization of Biotech ProductsNMPA Key Laboratory for Quality Research and Evaluation of Biological ProductsInstitute of Biological ProductsNational Institutes for Food and Drug ControlBejingChina national Engineering Technology Research Center for Combined vaccines WuhanChina Beijing Minhai Biotechnology Co LtdBeijingChina Taibang Biologic Group BeijingChina Changchun Institute of biological products Co. LtdChangchunChina Shanghai Institute of biological products Co LtdShanghaiChina China national Biotec Group Company Limited BeijingChina

With the continuous in-depth study of the interaction mechanism between viruses and hosts,the virus has become a promising tool in cancer *** fact,many oncolytic viruses with selectivity and effectiveness have been used in cancer *** enterovirus is one of the most convenient sources to generate oncolytic viruses,however,the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses.

关键词： damage enterovirus cancer

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Standardized neutralization antibody analytical procedure for clinical samples based on the AQbD concept

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2078-2080页

作者： Jianyang Liu Yu Bai Mingchen Liu Dejiang Tan Jing Li Zhongfang Wang Zhenglun Liang Miao Xu Junzhi Wang Qunying Mao national Institutes for Food and Drug Control BeijingChina NHC key laboratory of Research on quality and Standardization of Biotech products BeijingChina NMPA key laboratory for quality Research and evaluation of biological products BeijingChina Sinovac Life Science Co. Ltd.BeijingChina Guangzhou laboratory GuangzhouGuangdong ProvinceChina

Dear Editor,Vaccination is an effective strategy for controlling the COVID-19 pandemic and reducing the number of cases of hospitalization and deaths.1 Neutralizing antibody(Ntab)is one of the key indicators for evaluating the effectiveness of COVID-19 vaccines.2 Over 40 COVID-19 vaccines have been approved for emergency use,marketing,or marketing with conditions,and the available Ntab data from clinical trials have been published.

关键词： clinical QbD cases

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Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses

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Signal Transduction and Targeted Therapy 2022年第8期7卷 3069-3079页

作者： Qianqian Li Li Zhang Ziteng Liang Nan Wang Shuo Liu Tao Li Yuanling Yu Qianqian Cui Xi Wu Jianhui Nie Jiajing Wu Zhimin Cui Qiong Lu Xiangxi Wang Weijin Huang Youchun Wang Division of HIV/AIDS and Sex-transmitted Virus vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)WHO Collaborating Center for Standardization and Evaluation of BiologicalsNHC Key Laboratory of Research on Quality and Standardization of Biotech Products and NMPA Key Laboratory for Quality Research and Evaluation of Biological Products102629 BeijingChina Jiangsu Recbio Technology Co. Ltd.215300 TaizhouChina Graduate School of Chinese Academy of medical Sciences&Peking Union medical College No.9 Dongdan SantiaoDongcheng District100730 BeijingChina CAS key laboratory of Infection and Immunity CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of Sciences100101 BeijingChina

A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion *** evaluate its antigenicity relationship with other variants,antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern(VOCs)and variants of interest(VOIs)were cross-tested against pseudotyped *** neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens,and Omicron(BA.1)-elicited sera did not efficiently neutralize the other ***,a Beta or Omicron booster,when administered as the 4th dose 3-months after the 3rd dose of any of the variants,could elicit broad neutralizing antibodies against all of the current variants including Omicron *** analysis with 280 available antigen–antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential *** distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.

关键词： rational escape neutral

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SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5338-5352页

作者： Rongzhang He Xingyu Zheng Jian Zhang Bo Liu Qijie Wang Qian Wu Ziyan Liur Fangfang Chang Yabin Hu Ting Xie Yongchen Liu Jun Chen Jing Yang Shishan Teng Rui Lu Dong Pan You Wang Liting Peng Weijin Huang Velislava Terzieva Wenpei Liu Youchun Wang Yi-Ping Li Xiaowang Qu College of Basic medical Sciences Hengyang Medical SchoolUniversity of South China&MOE Key Lab of Rare Pediatric Diseases421001 HengyangChina Translational Medicine Institute The First People's Hospital of ChenzhouHengyang Medical SchoolUniversity of South China423000 ChenzhouChina The Central Hospital of Shaoyang 422000 ShaoyangChina Institute of Human Virology Zhongshan School of Medicineand Key Laboratory of Tropical Disease Control of Ministry of EducationSun Yat-sen University501180 GuangzhouChina School of Public Health University of South China421001 HengyangChina national Institutes for Food and Drug Control Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech ProductsKey Laboratory of Biological Product Quality Research and Evaluation of National Medical Products Administration102629 BejingChina laboratory of OMICs Technologies Institute of Biology and Immunology of Reproduction"Acad.Kiril Bratanov"BulgarianAcademyof SciencesSofia 1113Bulgaria

Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb)and B cell differentiation are tightly regulated by T follicular help (T_(FH)) cells. However, the longevity and functional role of T_(FH) cellsubsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection andinactivated vaccine elicited both spike-specific CXCR3^(+) T_(FH) cell and CXCR3^(-) T_(FH) cell responses, which showed distinct responsepatterns. Spike- specific CXCR3^(+) T_(FH) cells exhibit a dominant and more durable response than CXCR3^(-) T_(FH) cells that positivelycorrelated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3^(+) T_(FH) cell subset inducedby two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3^(+) T_(FH) cellshave a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3^(-) T_(FH)cells. In conclusion, the persistent and functional role of spike-specific CXCR3^(+) T_(FH) cells following SARS-CoV-2 infection andvaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. Thefindings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immunememory.

关键词： vaccine doses protective

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A Rapid Trace Analysis of GBS using the Specific Spectral Absorption of Chromogenic Culture Media

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Biomedical and Environmental Sciences 2023年第7期36卷 649-652页

作者： CHEN Yang ZHANG Yan Yan SHU Yao Gen Engineering Research Center of Clinical Functional Materials and Diagnosis and Treatment Devices of Zhejiang Province Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000ZhejiangChina Biomedical Engineering Wenzhou Medical UniversityWenzhou 325035ZhejiangChina College of Chemical Engineering Fuzhou UniversityFuzhou 350108FujianChina Research Center of Quantitative Detection Technology NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological ProductsWenzhou 325000ZhejiangChina Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou 325024ZhejiangChina

Group B streptococcus(GBS)is a Gram-positive,encapsulated bacterium that belongs to the group of pyogenic streptococci,and it is an asymptomatic colonizer of the digestive and genitourinary tracts of healthy human ***,it can cause severe invasive infections in neonates and immunocompromised *** the 1960s,GBS was identified as a leading cause of life-threatening neonatal infections[1,2].

关键词： urinary GBS neonatal

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The molecular determinants governing the immunogenicity of Japanese encephalitis live attenuated vaccines

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Signal Transduction and Targeted Therapy 2017年第1期2卷 251-257页

作者： Yuhua Li Yin Fu Xinyu Liu Huiqiang Yang Yongxin Yu Lili Jia Xuguang Li Aaron Farnsworth Junzhi Wang national Institutes for Food and Drug Control BeijingChina State key laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityCollaborative Innovation Center for Biotherapy Department of Viral Vaccine Chengdu Institute of Biological Products Co.LtdChina National Biotech GroupChengduChina Centre for Vaccine evaluation Biologics and Genetic Therapies DirectorateHealth Canada.

In the course of isolating the attenuated Japanese encephalitis vaccine SA14-14-2,two attenuated strains SA14-9-7 and SA14-5-3 were also obtained that elicited low antibody responses in humans(o10%and 62%,respectively)and exerted much weaker immune protection in animal challenge ***,the reason for these differences remains *** order to understand why SA14-14-2 is superior to SA14-9-7 and SA14-5-3,we employed a reverse genetics method to identify the key mutations in the virus genome that determine the immunogenicity of live attenuated Japanese encephalitis *** first sequenced the full genomic sequences of SA14-9-7 and SA14-5-3 and found mutations that changed four amino-acid base pairs when compared to the envelope gene of *** mutated the genome of SA14-14-2 to generate these mutations both singly(E-177,E-264,E-279 and E-315)and in combination(E-177/264,E-279/315 and E-177/264/279/315)and tested these mutants along with parental strains SA14-14-2,SA14-9-7 and SA14-5-3 for their immunogenicity in *** mice were immunized with SA14-9-7 and SA14-5-3,lower levels of neutralizing antibodies were generated compared with the immune response to ***,SA14-5-3 was more immunogenic than SA14-9-7,which replicated the results previously seen in *** mutations E-177,E-264,E-279 and E-315 diminished the immunogenicity of SA14-14-2 with E-264 and E-315,contributing the most to this *** mutant rJEV(E-177/E-264/E-279/E-315)containing all four point mutations exhibited the lowest immunogenicity with a seroconversion rate of 0 at an inoculation dose of 103 PFU(plaque-forming unit).We have identified the key amino acids in the envelope protein that account for the superior immunogenicity of SA14-14-2.

关键词： Japanese governing envelope

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The Representativeness of Air quality monitoring Sites in the Urban Areas of a Mountainous City

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Journal of Meteorological Research 2019年第2期33卷 236-250页

作者： Minjin MA Yue CHEN Fan DING Zhaoxia PU Xudong LIANG College of Atmospheric Sciences Lanzhou University College of Computer and Communication Lanzhou University of Technology Department of Atmospheric Sciences University of Utah State key laboratory of Severe Weather Chinese Academy of Meteorological Sciences

Lanzhou is a typical mountainous city with severe air pollution in northwestern China. This study uses hourly observational data of air pollutants at five air quality monitoring sites in Lanzhou from July to December 2015 to discuss data quality control and the representativeness of the monitoring sites(four urban sites and one suburban site). A fuzzy matrix is applied to study primary air pollutants. The results show that of the six routinely monitored pollutants,the primary pollutant is PM_10 during the study period. Based on lag correlation analysis and one-way analysis of variance, it is concluded that there are redundant observations at the four urban sites for the timely diffusion and transport of air pollutants from the same general area. The coefficient of divergence(COD) method is then used to evaluate the spatial distribution differences, and the primary air pollutant PM_10 shows differences at each site. COD can be used as a positive indicator to describe site representativeness. To evaluate the overall air pollution in the valley, correlation analysis is performed between the PM_10 concentration retrieved from aerosol optical depth satellite data and the concentration from the four urban monitoring sites. Among these, the correlation between the workers' hospital site data and the retrieval data is the highest, passing the 90% confidence level. A new representative evaluation model for air quality monitoring sites, R_s = 0.77 COD + 0.23R_(retrieval), is established by using COD and correlation coefficients between routine observations and satellite retrieval products. From this model, it can be concluded that the biological products institute site in Lanzhou is the most representative site for the evaluation of air pollution out of the four urban air quality monitoring sites from July to December 2015.

关键词： mountainous cities air quality monitoring site representativeness

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