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Innate and adaptive T cells in influenza disease

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Frontiers of Medicine 2018年第1期12卷 34-47页

作者： Simone Nfissing Sneha Sant Marios Koutsakos Kanta Subbarao Thi H.O. Nguyen Katherine Kedzierska Department of Microbiology and Immunology University of Melbourne at the Peter Doherty Institute for Infection and Immunity Parkville 3010 Victoria Australia World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity Melbourne 3000 Victoria Australia

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza- specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses （T cells and antibody-producing B cells） achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T- cells （MAIT cells, y~ T cells, and NKT cells） in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8＋ and CD4＋ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza innate T cells CD4＋ and CD8＋ T cells vaccination

Role of inactivated SARS-CoV-2 vaccine induced T cell responses in ameliorating COVID-19 severity

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Virologica Sinica 2023年第2期38卷 324-326页

作者： Hongming Huang Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Joint international Laboratory of infection and immunity Huazhong University of Science and TechnologyWuhan430022China

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine is one of the most effective weapons to fight the coronavirus disease 2019(COVID-19)pandemic(Lazarus et al.,2022).Among all SARS-CoV-2 vaccines generated on different platforms,those consisting of the inactivated virus,such as BBIBP-CorV and CoronaVac,have been frequently used(WHO,2023).By January 30,2023,92.9%of the entire,all-ages population had initiated vaccination and 90.6%had completed their primary series based on the whole population size reported in the seventh census of Chinese mainland(China CDC,2023).However,compared to SARS-CoV-2 mRNA vaccines,which can elicit extremely high quantities of anti-spike(S)antibodies,the levels of neutralizing antibodies induced by inactivated SARS-CoV-2 vaccines are quite lower and wane quickly(Peng et al.,2022;Lim et al.,2021).

关键词： vaccine severity acute

In search of a pan-coronavirus vaccine:next-generation vaccine design and immune mechanisms

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Cellular & Molecular Immunology 2024年第2期21卷 103-118页

作者： S.Cankat M.U.Demael L.Swadling Division of infection and immunity Institute of Immunity and TransplantationUniversity College LondonPears BuildingLondon NW32PPUK

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent history.In this review,we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus family.We will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2,MERS-CoV and the four seasonal coronaviruses(HCoV-OC43,NL63,HKU1 and 229E)in humans and the potential for future zoonotic coronaviruses.We will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine design.We will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer cross-protection.Finally,we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

关键词： Vaccine Coronavirus Cross-reactive immunity Cross-protection Universal

A Crowned Killer’s Ré sumeé: Genome, Structure, Receptors, and Origin of SARS-CoV-2

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Virologica Sinica 2020年第6期35卷 673-684页

作者： Shichuan Wang Mirko Trilling Kathrin Sutter Ulf Dittmer Mengji Lu Xin Zheng Dongliang Yang Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China institute for Virology University Hospital of EssenUniversity of Duisburg-EssenEssen 45147Germany Joint international Laboratory of infection and immunity Huazhong University of Science and TechnologyWuhan 430022China

The recent emergence and rapid global spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) pose an unprecedented medical and socioeconomic crisis, and the disease caused by it, Coronavirus disease 2019(COVID-19),was declared a pandemic by the World Health Organization(WHO) on March 11, 2020. Chinese scientists and physicians rapidly identified the causative pathogen, which turned out to be a novel betacoronavirus with high sequence similarities to bat and pangolin coronaviruses. The scientific community has ignited tremendous efforts to unravel the biological underpinning of SARS-CoV-2, which constitutes the foundation for therapy and vaccine development strategies. Here, we summarize the current state of knowledge on the genome, structure, receptor, and origin of SARS-CoV-2.

关键词： Coronavirus Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirus disease 2019(COVID-19) Genome Structure Receptor Origin

Recent advances in understanding T cell activation and exhaustion during HBV infection

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Virologica Sinica 2023年第6期38卷 851-859页

作者： Lu Wang Xiaoqing Zeng Zida Wang Ling Fang Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Joint international Laboratory of infection and immunity Huazhong University of Science and TechnologyWuhan430022China Central Sterile Supply Department Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Chronic hepatitis B virus(HBV)infection remains a major public health concern globally,and T cell responses are widely believed to play a pivotal role in mediating HBV clearance.Accordingly,research on the characteristics of HBV-specific T cell responses,from activation to exhaustion,has advanced rapidly.Here,we summarize recent developments in characterizing T cell immunity in HBV infection by reviewing basic and clinical research published in the last five years.We provide a comprehensive summary of the mechanisms that induce effective anti-HBV T cell immunity,as well as the latest developments in understanding T cell dysfunction in chronic HBV infection.Furthermore,we briefly discuss current novel treatment strategies aimed at restoring anti-HBV T cell responses.

关键词： Hepatitis B virus(HBV) T cell Immune therapy

Evaluation of Epstein-Barr Virus Salivary Shedding in HIV/AIDS Patients and HAART Use: A Retrospective Cohort Study

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Virologica Sinica 2018年第3期33卷 227-233页

作者： Yan Yan Yong Ren Renfang Chen Jing Hu Yongjia Ji Junyang Yang Jiayin Shen Lvyin Hu Hao Pei Jun Wang Yuanwang Qiu Hongzhou Lu Lihua Huang Center of Clinical Laboratory The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University Wuxi institute of Hepatology The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University The international Joint Research Laboratory for infection and immunity (China-Germany) The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University Wuxi Red Ribbon Care Center of China Red Cross The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University The international Joint Research Laboratory for infection and immunity (China-Germany) Wuxi School of MedicineJiangnan University Department of Infectious Diseases Shanghai Public Health Clinical Center Fudan University

Little data is available on the evaluation of the occurrence rates of Epstein-Barr virus(EBV) in saliva and relationship with highly active antiretroviral therapy(HAART) use in HIV/AIDS patients in China. We conducted a retrospective cohort study of EBV serological tests for HIV/AIDS patients who were treated in the hospitals for infectious diseases in Wuxi and Shanghai, China from May 2016 to April 2017. The EBV-seropositive samples were identified by ELISA. EBV-specific primers and probes were used for the quantitative detection of viral DNA from saliva via quantitative real-time polymerase chain reaction. CD4 cell counts of the HIV/AIDS patients were detected by a flow cytometry. A total of 372 HIV/AIDS patients were ultimately selected and categorized for this retrospective cohort study. For EBV IgG and IgM, the HIV/AIDS HAART use(H) and non-HAART use(NH) groups had significantly higher seropositive rates than the HIV-negative control group. The HIV/AIDS(NH) group had the highest seropositive rate(IgG, 94.27%; IgM, 68.98%) and the highest incidence of EBV reactivation or infection. For salivary EBV DNA-positive rates and quantities, the HIV/AIDS(H)(73.69%) and the HIV/AIDS(NH)(100%) groups showed significantly higher values than the HIV-negative control group(35.79%,[ twofold). Further, the salivary EBV DNA-negative population had significantly higher CD4 cell counts than the EBV DNA-positive population in the HIV/AIDS(H) group and the HIV/AIDS(NH) groups. Thus, HAART use is beneficial in decreasing the EBV salivary shedding in HIV/AIDS patients and indirectly decreases EBV transmission risk.

关键词：唾液病毒评估聚合酶链反应 EBV ELISA DNA 传染疾病

Helicobacter pylori and gastric cancer in the Middle East: A new enigma?

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World Journal of Gastroenterology 2010年第26期16卷 3226-3234页

作者： Nawfal R Hussein institute of infection Immunity and Inflammation and the Centre for Biomolecular Sciences University of Nottingham Nottingham NG7 2RD United Kingdom

The Middle East is the home of ethnic groups from three main backgrounds: Semitic (Arabs and Jews), Indo-European (Persians and Kurdish) and Turkic (Turkish and Turkmens). Its geographic location, which has been under continuous influences from Asia, Europe and Africa, has made it an ideal site for epidemiological studies on Helicobacter pylori (H. pylori) infection and genotyping. The gastric cancer rate differs in this region from very high in Iran (26.1/105) to low in Israel (12.5/105) and very low in Egypt (3.4/105). Epidemiological studies showed that the prevalence of H. pylori is almost similar in those countries with a high level of infection in childhood. Importantly, the frequency of vacA s1 and m1 regions and cagA+ genotypes were higher in non Semitic populations who inhabit the North than Semitic populations, the inhabitants of Southern parts of the Middle East. H. pylori infection prevalence, distribution pattern of virulence factors, diet and smoking could not have explained the difference in cancer rate. This reflects the multifactorial aetiology of gastric cancer and suggests that H. pylori infection does not always directly correlate with the risk for gastrointestinal disease, such as gastric cancer. Further detailed investigations and international comparative studies of each risk factor needto be performed to investigate whether this represents a true enigma.

关键词： Helicobacter pylori Middle East Gastric cancer dupA cagA vacA iceA

SARS-CoV-2-specific T cell responses wane profoundly in convalescent individuals 10 months after primary infection

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Virologica Sinica 2023年第4期38卷 606-619页

作者： Ziwei Li Tiandan Xiang Boyun Liang Jing Liu Hui Deng Xuecheng Yang Hua Wang Xuemei Feng Gennadiy Zelinskyy Mirko Trilling Kathrin Sutter Mengji Lu Ulf Dittmer Baoju Wang Dongliang Yang Xin Zheng Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China institute for Virology University Hospital of EssenUniversity of Duisburg-EssenEssen45147Germany Joint international Laboratory of infection and immunity Huazhong University of Science and TechnologyWuhan430022China

A key question in the coronavirus disease 2019(COVID-19)pandemic is the duration of specific T cell responses against the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)post primary infection,which is difficult to address due to the large-scale COVID-19 vaccination and re-exposure to the virus.Here,we conducted an analysis of the long-term SARS-CoV-2-specific T cell responses in a unique cohort of convalescent individuals(CIs)that were among the first to be infected worldwide and without any possible antigen re-exposure since then.The magnitude and breadth of SARS-CoV-2-specific T cell responses correlated inversely with the time that had elapsed from disease onset and the age of those CIs.The mean magnitude of SARS-CoV-2-specific CD4 and CD8 T cell responses decreased about 82%and 76%,respectively,over the time period of ten months after infection.Accordingly,the longitudinal analysis also demonstrated that SARS-CoV-2-specific T cell responses waned significantly in 75%of CIs during the follow-up.Collectively,we provide a comprehensive characterization of the long-term memory T cell response in CIs,suggesting that robust SARS-CoV-2-specific T cell immunity post primary infection may be less durable than previously expected.

关键词： COVID-19 SARS-CoV-2 T cell response Convalescence

Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H 1N 1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice

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Cellular & Molecular Immunology 2017年第6期14卷 511-520页

作者： I-Na Lu Sophie Farinelle Aurelie Sausy Claude P Muller Department of infection and immunity Luxembourg Institute of Health Esch-sur-Alzette L-4354 Luxembourg

The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2113-131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-a and IFN-7 production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor I~ sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H IN 1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune resoonse a^ainst influenza virus infection.

关键词： H1N1 hemagglutinin influenza T-cell receptor