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First clinical study of germline-targeting strategy: One step closer to a successful bnAb-based HIV vaccine

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The Innovation 2023年第1期4卷 36-37页

作者： caijun sun Teng Zuo Ziyu Wen School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China Laboratory of Immunoengineering Institute of Health and Medical TechnologyHefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China Key Laboratory of Tropical Disease Control(sun Yat-sen University) Ministry of EducationGuangzhou 511400China

The epidemic of human immunodeficiency virus type 1(HIV-1)remains amajor threat to global public health,with approximately 38 million people living with HIV-1 ***,a prophylactic vaccine against HIV-1 is not available *** a recent study,1 Leggat and colleagues reported the first-in-human test of a germline-targeting HIV-1 vaccine candidate,eOD-GT860-mer adjuvanted with ***,this strategy effectively activated the B cell precursors(germlines)of VRC01-class broadly neutralizing antibodies(bnAbs)in 97%(35 of 36)of vaccine recipients.

关键词： vaccine closer clinical

Antibody upstream sequence diversity and its biological implications revealed by repertoire sequencing

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Journal of Genetics and Genomics 2021年第10期48卷 936-945页

作者： Yan Zhu Xiujia Yang Cuiyu Ma Haipei Tang Qilong Wang Junjie Guan Wenxi Xie Sen Chen Yuan Chen Minhui Wang Chunhong Lan Deqiang sun Lai Wei caijun sun Xueqing Yu Zhenhai Zhang State Key Laboratory of Organ Failure Research National Clinical Research Center for Kidney DiseaseDivision of NephrologyNanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Bioinformatics School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Center for Precision Medicine Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Key Laboratory of Mental Health of the Ministry of Education Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceSouthern Medical UniversityGuangzhou 510515China Department of Nephrology Hainan Affiliated Hospital of Hainan Medical CollegeHaikou 570311China Department of Nephrology Hainan General HospitalHaikou 570311China Department of Center Laboratory The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China School of Public Health Sun Yat-sen UniversityShenzhen 510006China Division of Nephrology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China

The sequence upstream of the antibody variable region(antibody upstream sequence[AUS])consists of a 5′untranslated region(5′UTR)and a preceding leader *** sequence variations in AUS affect antibody engineering and PCR based antibody quantification and may also be implicated in mRNA transcription and ***,the diversity of AUSs remains *** 5′rapid amplification of cDNA ends and high-throughput antibody repertoire sequencing technique,we acquired full-length AUSs for human,rhesus macaque,cynomolgus macaque,mouse,and *** designed a bioinformatics pipeline and identified 3307 unique AUSs,corresponding to 3026 and 1457 unique sequences for 5′UTR and leader region,*** analysis indicated that 928(63.69%)leader sequences are novel relative to those recorded in the international ImMunoGeneTics information ***,leader sequences are more conserved than 5′UTR and seem to coevolve with their downstream V ***,single-nucleotide polymorphisms are position dependent for leader regions and may contribute to the functional reversal of the downstream V ***,the AUGs in AUSs were found to have little impact on gene *** together,our findings can facilitate primer design for capturing antibodies efficiently and provide a valuable resource for antibody engineering and molecule-level antibody studies.

关键词： Antibody upstream sequences 5′UTR Leader sequences Antibody repertoire sequencing Antibody repertoire

Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques

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Virologica Sinica 2021年第5期36卷 1197-1209页

作者： Chunxiu Wu Jin Zhao Ruiting Li Fengling Feng Yizi He Yanjun Li Runhan Huang Guangye Li Heng Yang Genhong Cheng Ling Chen Feng Ma Pingchao Li caijun sun State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health(GIBH)Chinese Academy of SciencesGuangzhou 510530China School of Public Health(Shenzhen) Sun Yat-Sen UniversityGuangdong 518107China Key Laboratory of Tropical Disease Control Sun Yat-Sen UniversityMinistry of EducationGuangzhou 514400China University of Chinese Academy of Sciences Beijing 100049China Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Suzhou Institute of Systems Medicine Suzhou 215123China Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos Angeles 90095USA Guangdong Landau Biotechnology Co.Ltd Guangzhou 510700China

Cholesterol-25-hydroxylase(CH25 H)and its enzymatic product 25-hydroxy cholesterol(25 HC)exert broadly antiviral activity including inhibiting HIV-1 ***,their antiviral immunity and therapeutic efficacy in a nonhuman primate model are ***,we report that the regimen of 25 HC combined with antiretroviral therapy(ART),provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques(RMs).Compared to the ART alone,this regimen more effectively controlled SIV replication,enhanced SIVspecific cellular immune responses,restored the ratio of CD4/CD8 cells,reversed the hyperactivation state of CD4^(+)T cells,and inhibited the secretion of proinflammatory cytokines by CD4^(^(+))and CD8^(+)T lymphocytes in chronically SIVinfected ***,the in vivo safety and the preliminary pharmacokinetics of the 25 HC compound were assessed in this RM *** together,these assessments help explain the profound relationship between cholesterol metabolism,immune modulation,and antiviral activities by 25 *** results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.

关键词： 25-hydroxycholesterol(25HC) HIV SIV Antiretroviral therapy(ART) Macaque

Safety and Immunogenicity of SARS-CoV-2 Vaccines in People Living With HIV:A Systematic Review and Meta-analysis of Real-World Studies

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Infectious Microbes & Diseases 2023年第4期5卷 159-166页

作者： Xueying Fan Yangguo Zhao Fan Wu Yue Yuan Bing Lang Di Yin Zhongliang Xu Shiqiang Jiang Huachun Zou Jianhui Yuan caijun sun School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenChina Nanshan District Center for Disease Control and Prevention ShenzhenChina School of Public Health(Shenzhen) Sun Yat-sen UniversityShenzhenChina Key Laboratory of Tropical Disease Control(sun Yat-sen University) Ministry of EducationGuangzhouChina

The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines in people living with HIV(PLWH)in real-world studies remain ***,we conducted a comprehensive systematic review and meta-analysis to address this *** search were conducted from PubMed,Web of Science and *** events following vaccination,the risk ratio(RR)of SARS-CoV-2–specific IgG seroconversion and the level of anti–SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group.A total of 10,582 PLWH from 22 studies were *** our analysis,the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy ***,there was a statistical difference after the second dose(RR,0.83;95%CI,0.71–0.98).The seroconversion rate of SARS-CoV-2 IgGantibodies in PLWH was significantly lower than that in the healthy control group(RR,0.94;95%CI,0.89–0.98;I2=80%,P<0.01).The anti–SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than those in the healthy control group(RR,0.91;95%CI,0.85–0.98;I2=81%,P<0.01).The safety and tolerance of COVID-19 vaccines in PLWHare ***,their immunogenicitymay be impaired to a certain extent,characterized by a lower IgGseroconversion rate and neutralizing antibody titers compared with healthy *** findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.

关键词： COVID-19 HIV immunogenicity safety vaccination meta-analysis

Acceptance and Factors Associated With Participation in Functional Cure–Related Trials Among People Living With HIV: A Cross-sectional Study in Southern China

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Infectious Microbes & Diseases 2024年第1期6卷 11-19页

作者： Zhaomin Deng Minjuan Shi Yue Yuan GuangjinCao Chunyan Wen Lijuan Chen Xueying Fan Linan Wu Jianhui Yuan Huachun Zou Linghua Li caijun sun School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenChina Department of Diseases Control Panyu District Center for Disease Control and PreventionGuangzhouChina Infectious Disease Center Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina Nanshan District Center for Disease Control and Prevention ShenzhenChina Key Laboratory of Tropical Disease Control(sun Yat-sen University) Ministry of EducationGuangzhouChina

HIV remains a global health challenge,and research efforts directed towards a functional cure require people living with HIV(PLHIV)in-volvement in clinical *** study assessed willingness to participate in HIV functional cure–related clinical trials and associated factors among PLHIV in Guangzhou,China,using a questionnaire survey *** analyzed responses from 718 questionnaires,finding that 71.2%were willing to participate in Phase Ⅲtrials,while 51.7%were willing to participate in Phase I trials and 42.9%expressed acceptability for analytic treatment *** logistic regression demonstrated that male PLHIV,those with awareness of functional cure,and PLHIV,who had been on antiretroviral therapy(ART)for less than 1 year,were more willing to partic-ipate in Phase Ⅲ*** with a body mass index greater than 24,and those without resistance to ART drug were more willing to participate in Phase I *** major motivations for participation in Phase Ⅲtrials were access to cutting-edge treatments(62.6%)and supporting research(55.3%).Safety was the main concern contributing to *** study revealed a high willingness to participate in HIV functional cure–related trials among PLHIV in Guangzhou,China,and willingness varied across different trial phases and was influenced by multiple *** study provides valuable references for future clinical trial recruitment strategies and public health policy formulation.

关键词： people living with HIV functional cure clinical trials willingness

Safety of SARS-CoV-2 vaccines:a systematic review and meta-analysis of randomized controlled trials

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Infectious Diseases of Poverty 2021年第4期10卷 92-92页

作者： Musha Chen Yue Yuan Yiguo Zhou Zhaomin Deng Jin Zhao Fengling Feng Huachun Zou caijun sun School of Public Health(Shenzhen) Sun Yat-Sen UniversityShenzhenChina

Background Various modalities of vaccines against coronavirus disease 2019(COVID-19),based on different platforms and immunization procedures,have been successively approved for marketing worldwide.A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass *** text A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials(RCTs).Data search was performed in PubMed,Embase,Cochrane library,Scopus,Web of Science,and *** articles were limited to RCTs on COVID-19 vaccines.A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization(AEFI)after vaccinating different COVID-19 *** risk ratios(RR)of total AEFI for inactivated vaccine,viral-vectored vaccine,and mRNA vaccine were 1.34[95%confidence interval(CI)1.11–1.61,P<0.001],1.65(95%CI 1.31–2.07,P<0.001),and 2.01(95%CI 1.78–2.26,P<0.001),*** significant differences on local and systemic AEFI were found between the first dose and second *** addition,people aged≤55 years were at significantly higher risk of AEFI than people aged≥56 years,with a pooled RR of 1.25(95%CI 1.15–1.35,P<0.001).Conclusions The safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination,with inactivated COVID-19 vaccines candidates having the lowest reported ***-term surveillance of vaccine safety is required,especially among elderly people with underlying medical conditions.

关键词： COVID-19 vaccine Safety Adverse events following immunization Randomized controlled trial Metaanalysis

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薄板坯连铸的粘结与预防

河南冶金 2007年第3期15卷 45-47页

作者：孙彩君杨杰唐山钢铁股份有限公司

本文分析了薄板坯粘结的影响因素,指出保护渣性能不合适、结晶器液位波动等是造成粘结的主要原因,由此提出相应的预防措施,使连铸的粘结发生率明显减少。

关键词：薄板坯连铸粘结预防

免疫应答在高致病性冠状病毒感染中的双重作用及其对新型疫苗研究的启示

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中华微生物学和免疫学杂志 2020年第6期40卷 410-417页

作者：闻子钰李彦君陈慕沙孙彩军中山大学公共卫生学院(深圳) 广州510006 中山大学热带病防治研究教育部重点实验室广州511400

近些年,冠状病毒(coronavirus,CoV)感染导致的疫情屡屡暴发,包括重症急性呼吸综合征(SARS)、中东呼吸综合征(MERS)以及新型冠状病毒肺炎(COVID-19),对公共卫生造成了持续威胁。CoV感染可诱发机体产生一系列免疫应答,包括固有免疫、体液... 详细信息

近些年,冠状病毒(coronavirus,CoV)感染导致的疫情屡屡暴发,包括重症急性呼吸综合征(SARS)、中东呼吸综合征(MERS)以及新型冠状病毒肺炎(COVID-19),对公共卫生造成了持续威胁。CoV感染可诱发机体产生一系列免疫应答,包括固有免疫、体液免疫、细胞免疫和黏膜免疫等。这些免疫应答不仅对机体抑制和消灭病毒入侵至关重要,在免疫病理和疾病重症化的过程中也扮演着重要角色。深入理解免疫应答在免疫保护和免疫病理中的双重作用,将有助于阐释CoV的致病机制和调控免疫保护和免疫病理间的平衡,促进CoV疫苗的成功研发。本文综述了免疫应答在高致病性CoV感染中的双重作用,对其在CoV新型疫苗研发中的启示作用进行了讨论和展望。

关键词：冠状病毒感染免疫应答疫苗

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卫星互联网安全风险及应对措施分析

天地一体化信息网络 2024年第1期5卷 95-101页

作者：谷欣单超孙才俊李珂田敏王瑞青中国星网网络创新研究院有限公司北京100029 之江实验室智能网络研究院浙江杭州311121 中电科网络安全科技股份有限公司北京100043

从阐述卫星互联网的系统组成和安全事件入手,综合分析卫星和载荷、卫星终端、信关站、运控中心、运营中心等实体对象的安全风险,接入链路、星间链路、馈电链路、测控链路、地面互联等通信链路安全风险,运营数据、通信内容监管、公众隐... 详细信息

从阐述卫星互联网的系统组成和安全事件入手,综合分析卫星和载荷、卫星终端、信关站、运控中心、运营中心等实体对象的安全风险,接入链路、星间链路、馈电链路、测控链路、地面互联等通信链路安全风险,运营数据、通信内容监管、公众隐私、数据违规出境等应用数据安全风险,以及新兴技术带来的安全风险挑战,并针对上述各种潜在的安全威胁提出相应的应对措施。最后对卫星互联网安全形势演变应关注的研究方向进行展望。

关键词：卫星互联网安全挑战安全风险应对措施