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Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris wenwei tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

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Single-cell RNA Sequencing Deciphers Immune Landscape of Human Recurrent Miscarriage

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Genomics, Proteomics & Bioinformatics 2021年第2期19卷 169-171页

作者： Chunyu Huang Yong Zeng wenwei tu Department of Paediatric and Adolescent Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation Fertility CenterShenzhen Zhongshan Urology HospitalShenzhen 518045China

Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune *** the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medawar,and the unique immunology of the maternal-fetal interface was recognized[1].Correct and precise interaction between mother and fetus plays an important role during pregnancy process,such as the apposition,adhesion,implantation,and growth of embryo in uterus[2].In 1991,Colbern and Main proposed that the maternal immune cells directly interact with placenta but not the fetus[3].Therefore,information concerning the cross-talk between maternal immune cells and placenta during normal pregnancy will provide clues to explore the underlying mechanism of pathological *** cells,such as natural killer(NK),macrophage,T,and dendritic cells,have been demonstrated to play important roles during normal pregnancy[4].With the development of single-cell RNA sequencing(scRNA-seq)technologies,researchers are devoted to providing a whole picture about the immune cellular composition and inter-cellular communication events during normal pregnancy[5,6].These foundational studies reveal that immune cell subsets,which are classified based on different markers at high resolution,exert specific function during pregnancy ***,the panoramic analysis of immune subsets at high resolution in pathological pregnancy remains lacking.

关键词： fetus Immune mother

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CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD41 regulatory T cells

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Cellular & Molecular Immunology 2010年第1期7卷 44-50页

作者： Jian Zheng Yinping Liu Yu-Lung Lau wenwei tu Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina Joint Research Centre West China Second University HospitalSichuan University and Faculty of MedicineUniversity of Hong KongChengduChina

CD4^(+)regulatory T cells(Tregs)play an important role in maintaining immune tolerance by suppressing pathologic immune responses.,The generation of large numbers of antigen-specific Tregs ex vivo is critical for the development of clinical immunotherapy based on the adoptive transfer of *** CD40-activated B cells(CD40-B)and immature dendritic cells(imDCs)have been used as professional antigen-presenting cells(APCs)to generate antigen-specific ***,the efficiencies of CD40-B and imDCs to generate CD4^(+)Tregs have not been compared directly and the mechanism driving the generation of these Tregs remains largely *** this study,we found that CD40-B exhibited mature phenotypes and were more able to induce and expand CD4^(high)"CD25^(+)Tregs than ***,Tregs induced by CD40-B had greater suppressive capacity than those induced by *** generation of CD4^(high)CD25^(+)Tregs by CD40-B and imDCs is cell-cell contact dependent and partially relies on the expression of human leukocyte antigen(HLA)-DR and CD80/*** in CD4^(high)CD25^(+)Treg generation efficiency were largely explained by the production of endogenous IL-2 by *** results suggest that CD40-B is better able to generate large numbers of antigen-specific Tregs than ***,using CD40-B to generate Tregs may accelerate the clinical use of Treg-based immunotherapy in the treatment of allograft rejection,graft versus host disease(GVHD)and autoimmune diseases.

关键词： B cells immature DC Treg IL-2

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Exosomes derived from nasopharyngeal carcinoma cells induce IL-6 production from macrophages to promote tumorigenesis

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Cellular & Molecular Immunology 2021年第2期18卷 501-503页

作者： Xiwei Wang Zheng Xiang George Sai-Wah Tsao wenwei tu Department of Paediatrics&Adolescent Medicine Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina

Chronic inflammation in the tumor microenvironment can promotes *** immune cells,including macrophages,can infiltrate into the tumor microenvironment and secrete abundant inflammatory cytokines.1 Interleukin-6(IL-6)is a major inflammatory cytokine that is widely involved in the tumorigenesis of many cancers,including nasopharyngeal carcinoma(NPC).2 In NPC patients,serum IL-6 was elevated and positively correlated with poor prognosis,suggesting that IL-6 may play a critical role in NPC progression.2,3 Indeed,previous studies demonstrated that IL-6 could activate signal transducer and activator of transcription 3(STAT3)and promote the proliferation,migration,and invasion of NPC cells.2 However,the mechanism underlying the upregulation of IL-6 in NPC remains elusive.

关键词： tumorigenesis nasopharyngeal invasion

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Avian influenza virus directly infects human natural killer cells and inhibits cell activity

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Virologica Sinica 2017年第2期32卷 122-129页

作者： Huawei Mao Yinping Liu Sin Fun Sia JS Malik Peiris Yu-Lung Lau wenwei tu Department of Paediatrics The University of Hong Kong - Shenzhen Hospital Shenzhen 518000 China Department of Paediatrics & Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China Department of Microbiology The University of Hong Kong Hong Kong SAR China Shenzhen Engineering Laboratory of PID Diagnosis & Therapy Technology Shenzhen 518000 China

Natural killer(NK) cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitted in the early phase of virus infection. Evasion of host innate immunity including NK cells is critical for the virus to expand and establish a successful acute infection. Previously,we showed that human influenza H1N1 virus infects NK cells and induces cell apoptosis, as well as inhibits NK cell activity. In this study, we further demonstrated that avian influenza virus also directly targeted NK cells as an immunoevasion strategy. The avian virus infected human NK cells and induced cell apoptosis. In addition, avian influenza virion and HA protein inhibited NK cell cytotoxicity. This novel strategy has obvious advantages for avian influenza virus, allowing the virus sufficient time to expand and subsequent spread before the onset of the specific immune response. Our findings provide an important clue for the immunopathogenesis of avian influenza,and also suggest that direct targeting NK cells may be a common strategy used by both human and avian influenza viruses to evade NK cell immunity.

关键词：生来的杀手(NK ) 房间鸟的流行性感冒病毒(AIV ) immunoevasion 方向感染抑制 cytotoxicity

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CD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1746-1755页

作者： Yujun Pei Kun Wen Zheng Xiang Chunyu Huang Xiwei Wang Xiaofeng Mu Liyan Wen Yinping Liu wenwei tu Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Influenza epidemics and pandemics are constant threats to global public *** strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection,the efficacy of these strategies is limited by the highly frequent mutations in the viral genome and the emergence of drug-resistant *** previous study indicated that boosting the immunity of human Vγ9Vδ2-T cells with the phosphoantigen pamidronate could be a therapeutic strategy to treat seasonal and avian influenza virus ***,one notable drawback ofγδ-T cell-based immunotherapy is the rapid exhaustion of proliferation and effector responses due to repeated treatments with ***,we found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic ***137^(+)Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137−counterparts in vitro and in Rag2^(-/-)γc^(-/-)*** further demonstrated that CD137 costimulation was essential for Vγ9Vδ2-T cell activation,proliferation,survival and effector *** humanized mice reconstituted with human peripheral blood mononuclear cells,CD137 costimulation with a recombinant human CD137L protein boosted the therapeutic effects of pamidronate against influenza *** study provides a novel strategy of targeting CD137 to improve the efficacy of Vγ9Vδ2-T cell-based immunotherapy.

关键词： CD137 influenza drugs

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yδ-T cells： an unpolished sword in human anti-infection immunity

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Cellular & Molecular Immunology 2013年第1期10卷 50-57页

作者： Jian Zheng Yinping Liu Yu-Lung Lau wenwei tu Department of Pediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China

yδ-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of yδ-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis, yδ-T cells have both ＇innate＇ and ＇adaptive＇ characteristics in the immune response, and their *** activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in yδ-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different yδ-T cell subpopulations under specific conditions, yδ-T cell-based therapy has great potential for the treatment of infectious diseases.

关键词： yδ-T cells infection immunity human

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人γδ-T细胞抗病毒及抗肿瘤效应特质（英文）

人γδ-T细胞抗病毒及抗肿瘤效应特质（英文）

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第十届全国免疫学学术大会

作者： wenwei tu Department of Pediatrics & Adolescent Medicine Laboratory for Translational Immunology Li Ka Shing Faculty of Medicine University of Hong Kong

γδ-T cells represent for a small population of immune cells,but play indispensible role in host defense against exogenous pathogen,immune surveillance on endogenous pathogenesis and even homeostasis of immune *** activation and expansion of γδ-T cells are generally observed in diverse human diseases and correlate with the progress and prognosis of diseases.γδ-T cells have both"innate"and"adaptive"like characteristics in immune responses,and their antiviral

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From Bench to Bedside:Applications of Humanized Mice in the Research of Translational Immunology

From Bench to Bedside:Applications of Humanized Mice in the ...

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第九届全国免疫学学术大会

作者： wenwei tu Laboratory for Translational Immunology Department of Pediatrics & Adolescent MedicineLi Ka Shing Faculty of Medicinethe University of Hong Kong

Animal models have provided important fundamental insights into biological and immunological processes that are common between ***,many aspects of mammalian biological systems,particularly their immune systems,are spe...

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Targeting human γδ-T cells:A potential novel strategy to treat human and avian influenza diseases

Targeting human γδ-T cells:A potential novel strategy to t...

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第八届全国免疫学学术大会

作者： wenwei tu Department of Paediatrics & Adolescent Medicine Research Center of Infection & Immunology The University of Hong Kong

Influenza is an acute respiratory virus infection associated with significant morbidity and mortality that continues to threaten global public *** are few antiviral drugs for treating influenza,and the emergence of antiviral resistance has further limited the available therapeutic ***,antivirals are not invariably effective in severe influenza,such as that caused by H5N1 *** development of alternative strategies to contain virus infection by boosting innate immunity has obvious advantages for the treatment of influenza without the risk of encouraging antiviral *** way to enhance innate immunity is to stimulate natural killer(NK)cell activity but our recent studies demonstrated that influenza virus can use a novel strategy to evade NK cell immunity by directly killing NK cells and inhibiting NK cell *** therefore looked for an alternative way of augmenting innate ***γδ-T cells are thought to represent

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