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Advances in Research on COVID-19 Vaccination for People Living with HIV

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Infectious Diseases & Immunity 2022年第4期2卷 213-218页

作者： Junyan Jin xiuwen wang Raphael Carapito Christiane Moog Bin Su Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Laboratoire d’ImmunoRhumatologie Moléculaire Institut National de la Santéet de la Recherche Médicale(INSERM)UMR_S 1109Institut Thématique Interdisciplinaire(ITI)de Médecine de Précision de StrasbourgTransplantex NGFacultéde MédecineFédération Hospitalo-Universitaire OMICAREFédération de Médecine Translationnelle de Strasbourg(FMTS)Universitéde StrasbourgStrasbourg 67000France

Introduction In December 2019,multiple cases of aggravated pneumonia of unidentified origin were reported inWuhan,China.These were confirmed to be caused by a novel coronavirus.The World Health Organization(WHO)named the disease coronavirus disease 2019(COVID-19).The International Committee on Taxonomy of Viruses officially identified the novel virus severe acute respiratory syndrome coronavirus 2(SARSCoV-2).[1]Although China is now a low endemic areawith a downward trend in the number of confirmed and suspected cases,[2]the threat of the COVID-19 pandemic remains critical.By mid-March 2022,the cumulative number of reported confirmed cases of COVID-19 worldwide exceeded 450 million,with more than 6 million deaths.[3]Since there is no specific therapeutic drug for the treatment of COVID-19,it is important to control the epidemic by actively promoting SARS-CoV-2 vaccination globally,reducing the risk of viral transmission and the incidence of severe COVID-19,thus improving prognoses.[4]

关键词： HIV SARS-CoV-2 COVID-19 Vaccination PLWH

Glut1 expression on CD8^(dim)T cells is associated with immune recovery in HIV-1-infected individuals

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Chinese Medical Journal 2023年第24期136卷 2999-3001页

作者： xiuwen wang Xin Zhang Xiaofan Lu Zhen Li Lifeng Liu Hao Wu Tong Zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China

To the Editor:Immune non-responders(INRs),who account for approximately 10-40%of human immunodeficiency virus(HIV)-infected individuals,have received effective treatment and exhibit persistent suppression of viral replication,but their CD4^(+)T-cell counts are not restored.They are likely to have an increased risk of non-acquired immunodeficiency syndrome(AIDS)-related morbidity and mortality compared with immune responders(IRs).[1]CD8^(+)T cells play an important role in viral infection,and the functional properties of circulating CD8^(+)T cells have been associated with immune control of HIV.High CD8^(+)T-cell counts are beneficial for persistent viral decay and CD4 T-cell recovery in immune-restored patients during long-term antiretroviral therapy(ART).[2]Two subsets of CD8^(+)T cells have been identified according to their intensity of CD8 expression:CD8^(bri)and CD8^(dim)T lymphocytes.It was demonstrated that CD3^(+)CD8^(dim)T cells,with weaker function than CD3^(+)CD8^(bri)T cells,were associated with disease progression during HIV infection.[3]However,dynamic changes in the numbers of CD8^(bri)and CD8^(dim)T cells in INRs and IRs before and after ART have not yet been reported.

关键词： infected mortality likely

Durable natural killer cell response after three doses of SARS-CoV-2 inactivated vaccine in HIV-infected individuals

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Chinese Medical Journal 2023年第24期136卷 2948-2959页

作者： Xiaodong Yang xiuwen wang Xin Zhang Haifeng Ding Hu wang Tao Huang Guanghui Zhang Junyi Duan Wei Xia Bin Su Cong Jin Hao Wu Tong Zhang Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Tian Yuan Studio Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer(NK)cell response in people living with human immunodeficiency virus(PLWH)and healthy individuals.Methods:Forty-seven PLWH and thirty healthy controls(HCs)inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study.The effect of SARS-CoV-2 vaccine on NK cell frequency,phenotype,and function in PLWH and HCs was evaluated by flow cytometry,and the response of NK cells to SARS-CoV-2 Omicron Spike(SARS-2-OS)protein stimulation was also evaluated.Results:SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH,which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine.However,in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers.Additionally,the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0,4 and 12 weeks,but the percentage of CD16^(+)NK cells in PLWH was significantly higher than that in HCs at 2,4 and 12 weeks after the third dose of vaccine.Interestingly,the frequency of CD16^(+)NK cells was significantly negatively correlated with the proportion of CD107a^(+)NK cells in PLWH at each time point after the third dose.Similarly,this phenomenon was also observed in HCs at 0,2,and 4 weeks after the third dose.Finally,regardless of whether NK cells were stimulated with SARS-2-OS or not,we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.Conclusions:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells,indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune respo

关键词： HIV SARS-CoV-2 inactivated vaccine COVID-19 Omicron variant NK cell response Immunologic memory

Changing roles of CD3^(+)CD8^(low) T cells in combating HIV-1 infection

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Chinese Medical Journal 2023年第4期136卷 433-445页

作者： Xin Zhang xiuwen wang Ling Qin Xiaofan Lu Zhiying Liu Zhen Li Lin Yuan Rui wang Junyan Jin Zhenglai Ma Hao Wu Yonghong Zhang Tong Zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Research Center for Biomedical Resources Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(

关键词： Acute human immunodeficiency virus-1 infection HIV CD3^(+)CD8^(low)T cells Immune activation Programmed cell death protein 1 T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains

Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8^(+)T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine

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Chinese Medical Journal 2023年第24期136卷 2938-2947页

作者： Junyan Jin xiuwen wang Yongzheng Li Xiaodong Yang Hu wang Xiaoxu Han Jin Sun Zhenglai Ma Junyi Duan Guanghui Zhang Tao Huang Tong Zhang Hao Wu Xin Zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Biomedical Pioneering Innovation Center(BIOPIC) Peking UniversityBeijing 100871China Tian Yuan Studio Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor activity.However,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated vaccines.Methods:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this study.The amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third dose.Results:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in PLWH.Interestingly,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay.Compared with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs.Additionally,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T cells.However,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was insignificant at 4W and 12W,except at 0W.Conclusio

关键词： HIV TIGIT T-lymphocytes SARS-CoV-2 Booster vaccination Immunity

Investigation and analysis of leveling deformation anomaly at Daixian station in Shanxi

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Geodesy and Geodynamics 2017年第2期8卷 130-135页

作者： xiuwen wang Earthquake Administration of Shanxi Province Taiyuan 030021 China State Key Observatory of Shanxi Rift System Taiyuan 030025 China Earthquake Administration of Daixian County Daixian 034200 China

The leveling measurements at Daixian station appeared increasing trend since March 25, 2013, which is credible, showing normal fault activity. According to the environmental survey, it contains some interference factors： first, the wind is big when the leveling measures in the afternoon, which has certain influence on the measurement results, but the impact is random and should be near the base value and not appear a trend. Second, the point BM3 was maintained during Sep. to Oct. in 2012 and occurred cracks in 2013, showing that the poor stability around the point. In addition, the change of recorded program is only to change the way of data record and can not affect the observation results during the same period.

关键词： Daixian station in Shanxi Leveling measurement Anomaly Investigation

High-adaption locomotion with stable robot body for planetary exploration robot carrying potential instruments on unstructured terrain

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Chinese Journal of Aeronautics 2021年第5期34卷 652-665页

作者： Kang XU Shoukun wang Junzheng wang xiuwen wang Zhihua CHEN Jinge SI School of Automation Beijing Institute of Technology.Beijing 100081China Key Laboratory of Intelligent Control and Decision of Complex System Beijing Institute of TechnologyBeijing 100081China Key Laboratory Ministry of Industry and Information Technology Beijing Institute of TechnologyBeijing 100081China

There is a strong demand for Planetary Exploration Mobile robots(PEMRs)that have the capability of the traversability,stability,efficiency and high load while tackling the specialized tasks on planet surface.In this paper,an electric parallel wheel-legged hexapod robot which has high-adaption locomotion on the unstructured terrain is presented.Also,the hybrid control framework,which enables robot to stably carry the heavy loads as well as to traverse the uneven terrain by utilizing both legged and wheeled locomotion,is also proposed.Based on this framework,robot controls the multiple DOF leg for performing high-adaption locomotion to negotiate obstacles via Gait Generator(GG).Additionally,by using Whole-Body Control(WBC)of framework,robot has the capability of flexibly accommodating the uneven terrain by Attitude Control(AC)kinematically adjusting the length of legs like an active suspension system,and by Force/torque Balance Control(FBC)equally distributing the Ground Reaction Force(GRF)to maintain a stable body.The simulation and experiment are employed to validate the proposed framework with the physical system in the planetary analog environments.Particularly,to smoothly demonstrate the performance of robot transporting heavy loads,the experiment of carrying 3-person load of about 240 kg is deployed.

关键词： Attitude control Gait generation High-adaption locomotion Obstacle avoidance Planetary exploration robot

Retrospective analysis of results of treatment for nasopharyngeal carcinoma in Macao

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Chinese Journal of Cancer Research 2014年第2期26卷 148-158页

作者： Huiqin Dou Dongyan Hu Chileong Lam Yunsheng Liu xiuwen wang Wendong Zhang Department of Stomatology Qilu Hospital of Shandong University Department of Clinical Oncology Qilu Hospital of Shandong University Department of Clinical Oncology Conde S.Januario General Hospital

Background： Nasopharyngeal carcinoma （NPC） is a common malignancy in Southeast Asia, however, a full consensus has not yet been reached as to the value of comprehensive treatment for NPC. This study was designed to evaluate the epidemiological characteristics of NPC and their prognostic value, as well as the long-term efficacy of NPC treatment. Patients and methods： A total of 248 patients, with different stages of NPC, were included in this study. Results： The 5-year overall survival （OS） rates for patients in stages I, II, lII and IV were 90.48%, 76.71%, 76.89% and 33.87%, respectively （P=0.000）, while the respective 5-year progression-free survival （PFS） rates were 85.15%, 72.36%, 63.88% and 26.26% （P=0.000）. The respective 5-year OS rates, according to stage, for the group that received radiotherapy combined with chemotherapy and for the group that received radiotherapy only were as follows： stages I and II, 81.67% and 79.59% （P=0.753）; stage III, 79.91% and 70.38% （P=0.143）; stage IV,, 35.22% and 0% （P=0.000）. The respective 5-year PFS rates in these groups were as follows： stages I and II, 75.83% and 74.98% （P=0.814）; stage III, 74.08% and 42.25% （P=0.027）; stage IV,, 27.31% and 0% （P=0.000）. Conclusions： Clinical staging appears to be the most important prognostic factor for NPC. As the stage number increases, both the 5-year OS and PFS significantly decrease. Adding chemotherapy to radiotherapy was not advantageous for patients with stage I or II NPC, however the addition of chemotherapy to radiotherapy significantly improved OS and PFS in patients with stage IV NPC. The addition of chemotherapy improved PFS, but not OS in patients with stage III NPC.

关键词： Nasopharyngeal carcinoma （NPC） treatment retrospective analysis Macao

Th17 Cells in autoimmune diseases

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Frontiers of Medicine 2015年第1期9卷 10-19页

作者： Lei Han Jing Yang xiuwen wang Dan Li Ling Lv Bin Li Division of Rheumatology Huashan Hospital Fudan University Shanghai 200040 China Key Laboratory of Molecular Virology and Immunology Unit of Molecular Immunology Institut Pasteur of Shanghai Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

Th17 cells are a new subset of CD4^＋ T cells fungi. Accumulating evidence suggests that Tb17 cells involved in the clearance of extracellular pathogens and and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren＇s syndrome, inflammatory bowel disease, and multiple sclerosis.

关键词： IL-17 Thl 7 cells RORγt autoimmune diseases posttranslational modification inhibitors