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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 necessary.Fractional 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 unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.Humoral 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,respectively.Results 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 inferior.For 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 IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion 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 immunogenicity of inactivated vaccines.

关键词： CoronaVac Coronavirus disease 2019 immunity Intradermal Vaccine

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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the peter doherty institute for infection and immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

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Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

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Cellular & Molecular Immunology 2022年第3期19卷 421-431页

作者： Kevin Man Axel Kallies Ajithkumar Vasanthakumar peter doherty institute for infection and immunity MelbourneVICAustralia Department of Microbiology and Immunology University of MelbourneMelbourneVICAustralia Olivia Newton-John Cancer Research institute MelbourneVICAustralia

Glucose is a vital source of energy for all mammals.The balance between glucose uptake,metabolism and storage determines the energy status of an individual,and perturbations in this balance can lead to metabolic diseases.The maintenance of organismal glucose metabolism is a complex process that involves multiple tissues,including adipose tissue,which is an endocrine and energy storage organ that is critical for the regulation of systemic metabolism.Adipose tissue consists of an array of different cell types,including specialized adipocytes and stromal and endothelial cells.In addition,adipose tissue harbors a wide range of immune cells that play vital roles in adipose tissue homeostasis and function.These cells contribute to the regulation of systemic metabolism by modulating the inflammatory tone of adipose tissue,which is directly linked to insulin sensitivity and signaling.Furthermore,these cells affect the control of thermogenesis.While lean adipose tissue is rich in type 2 and anti-inflammatory cytokines such as IL-10,obesity tips the balance in favor of a proinflammatory milieu,leading to the development of insulin resistance and the dysregulation of systemic metabolism.Notably,anti-inflammatory immune cells,including regulatory T cells and innate lymphocytes,protect against insulin resistance and have the characteristics of tissue-resident cells,while proinflammatory immune cells are recruited from the circulation to obese adipose tissue.Here,we review the key findings that have shaped our understanding of how immune cells regulate adipose tissue homeostasis to control organismal metabolism.

关键词： adipose tissue immune cells metabolism

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South Asian dairy smallholders: A scoping review of practices and zoonoses

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Asian Pacific Journal of Tropical Medicine 2023年第10期16卷 446-452页

作者： Emily Schembri Angus J D Campbell Juan Pablo Villanueva-Cabezas Melbourne School of Population and Global Health The University of MelbourneVictoriaAustralia The Nossal institute for Global Health The University of MelbourneVictoriaAustralia The peter doherty institute for infection and immunity The University of Melbourne and the Royal Melbourne HospitalVictoriaAustralia

Objective: To identify and discuss on-farm management practices linked to bacterial zoonosis risk in smallholder dairy farmers in South Asia. Methods: This scoping review was conducted as per the PRISMA-ScR guidelines. Five hundred and two publications were retrieved from five online databases using a comprehensive search strategy. Studies were selected if they discussed a farm management practice which impacted human health within a South Asian country. Results: Twenty-two studies were included. Seven management practices relevant to farmers, livestock and their shared environment were identified including raw milk consumption, farm hygiene management, personal protective equipment uses, animal vaccination, cleaning udders, hand washing and disposal of afterbirth materials. Preventive practices were found to be utilized at lower frequencies compared to risk increasing practices. Awareness of bacterial zoonoses is particularly low within the region. Conclusions: Based on the results of this review, it was determined that improving farmer awareness of bacterial zoonotic diseases may favor several of the presented leverage points within the South Asian smallholder dairy system. Relying on formal school education to improve this awareness may not solve this problem, instead, more focus on accessible and affordable zoonoses education and farming programs is required.

关键词： Management practices Zoonoses Dairy Smallholder system

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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

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Mpox (monkeypox) knowledge, concern, willingness to change behaviour, and seek vaccination: Results of a national cross-sectional survey

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Sexual Health 2023年第5期20卷 403-410页

作者： Macgibbon J. Cornelisse V.J. Smith A.K.J. Broady T.R. Hammoud M.A. Bavinton B.R. Heath-Paynter D. Vaughan M. Wright E.J. Holt M. Centre for Social Research in Health UNSW Sydney Sydney NSW Australia Kirby institute UNSW Sydney Sydney NSW Australia NSW Health Sydney NSW Australia Health Equity Matters Sydney NSW Australia ACON Sydney NSW Australia Department of Infectious Diseases Alfred Hospital and Central Clinical School Monash University Melbourne VIC Australia Burnet institute Melbourne VIC Australia The peter doherty institute of infection and immunity Melbourne VIC Australia

Background: In mid-2022, a global mpox (formerly 'monkeypox') outbreak affecting predominantly gay and bisexual men emerged in non-endemic countries. Australia had never previously recorded mpox cases and there was no prior research on knowledge or attitudes to mpox among gay and bisexual men across Australia. Methods: We conducted a national, online cross-sectional survey between August 2022 and September 2022. Participants were recruited through community organisation promotions, online advertising, and direct email invitations. Eligible participants were gay, bisexual or queer; identified as male (cisgender or transgender) or non-binary; aged 16 years or older; and lived in Australia. The main outcome measures were: knowledge and concern about mpox; recognition of mpox symptoms and transmission routes; vaccination history; acceptability of behavioural changes to reduce mpox risk, and willingness to be vaccinated. Results: Of 2287 participants, most participants were male (2189/2287; 95.7%) and gay (1894/2287; 82.8%). Nearly all had heard about mpox (2255/2287; 98.6%), and the majority were concerned about acquiring it (1461/2287; 64.4%). Most of the 2268 participants not previously diagnosed with mpox correctly identified skin lesions (2087; 92%), rash (1977; 87.2%), and fever (1647; 72.6%) as potential symptoms, and prolonged and brief skin-To-skin contact as potential ways to acquire mpox (2124, 93.7%; and 1860, 82%, respectively). The most acceptable behavioural changes were reducing or avoiding attendance at sex parties (1494; 65.9%) and sex-on-premises venues (1503; 66.4%), and having fewer sexual partners (1466; 64.6%). Most unvaccinated and undiagnosed participants were willing to be vaccinated (1457/1733; 84.1%). Conclusions: People at risk of mpox should be supported to adopt acceptable risk reduction strategies during outbreaks and to seek vaccination. © 2023 CSIRO. All rights reserved.

关键词： attitudes Australia gay and bisexual men men who have sex with men monkeypox mpox sexual behaviour sexual practice sexually transmissible infection vaccination vaccine

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Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

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Signal Transduction and Targeted Therapy 2023年第1期8卷 266-275页

作者： Xiaofeng Mu Carolyn A.Cohen Daniel Leung Jaime S.Rosa Duque Samuel M.S.Cheng Yuet Chung Howard H.W.Wong Amos M.T.Lee Wing Yan Li Issan Y.S.Tam Jennifer H.Y.Lam Derek H.L.Lee Sau Man Chan Leo C.H.Tsang Karl C.K.Chan John K.C.Li Leo L.H.Luk Sara Chaothai Kelvin K.H.Kwan Nym Coco Chu Masashi Mori Trushar Jeevan Ahmed Kandeil Richard JWebby Wenwei Tu Sophie A.Valkenburg Malik Peiris Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina HKU-Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Infectious Diseases St Jude Children’s Research HospitalMemphisTNUSA Department of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Centre for Immunology&infection C2i Hong KongChina

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies,but immune responses conferring this protection are not yet elucidated.In this analysis,our study(NCT04800133)aims to evaluate the humoral and cellular responses against wild-type and Omicron(BA.1,BA.2 and/or BA.5)SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents.At 5 months after 2 doses,S IgG,S IgG Fc receptor-binding,and neutralising antibody responses waned significantly,yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses.The antibody responses and S-specific IFN-γ^(+)and IL-2^(+)CD8^(+)T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2.Compared to adults,humoral responses for the third dose were non-inferior or superior in adolescents.The S-specific IFN-γ^(+)and IL-2^(+)CD4^(+)and CD8^(+)T cell responses in adolescents and adults were comparable or non-inferior.Interestingly,after 3 doses,adolescents had preserved S IgG,S IgG avidity,S IgG FcγRIIIa-binding,against Omicron BA.2,as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1,BA.2 and BA.5.Sera from 100 and 96%of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1.Our study found high antibody and T cell responses,including potent cross-variant reactivity,after three doses of BNT162b2 vaccine in adolescents in its current formulation,suggesting that current vaccines can be protective against symptomatic Omicron disease.

关键词： doses neutral protective

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Understanding the impact of disease and vaccine mechanisms on the importance of optimal vaccine allocation

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Infectious Disease Modelling 2023年第2期8卷 539-550页

作者： Isobel R.Abell James M.McCaw Christopher M.Baker School of Mathematics and Statistics The University of MelbourneMelbourneAustralia Melbourne Centre for Data Science The University of MelbourneMelbourneAustralia Centre for Epidemiology and Biostatistics Melbourne School of Population and Global HealthThe University of MelbourneMelbourneAustralia peter doherty institute for infection and immunity The Royal Melbourne Hospital and the University of MelbourneMelbourneAustralia Centre of Excellence for Biosecurity Risk Analysis The University of MelbourneMelbourneAustralia

Vaccination is an important epidemic intervention strategy.However,it is generally unclear how the outcomes of different vaccine strategies change depending on population characteristics,vaccine mechanisms and allocation objective.In this paper we develop a conceptual mathematical model to simulate strategies for pre-epidemic vaccination.We extend the SEIR model to incorporate a range of vaccine mechanisms and disease characteristics.We then compare the outcomes of optimal and suboptimal vaccination strategies for three public health objectives(total infections,total symptomatic infections and total deaths)using numerical optimisation.Our comparison shows that the difference in outcomes between vaccinating optimally and suboptimally depends on vaccine mechanisms,disease characteristics,and objective considered.Our modelling finds vaccines that impact transmission produce better outcomes as transmission is reduced for all strategies.For vaccines that impact the likelihood of symptomatic disease or dying due to infection,the improvement in outcome as we decrease these variables is dependent on the strategy implemented.Through a principled model-based process,this work highlights the importance of designing effective vaccine allocation strategies.We conclude that efficient allocation of resources can be just as crucial to the success of a vaccination strategy as the vaccine effectiveness and/or amount of vaccines available.

关键词： Mathematical modelling Epidemiology

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Local heroes or villains:tissue-resident memory T cells in human health and disease

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Cellular & Molecular Immunology 2020年第2期17卷 113-122页

作者： S.C.Sasson C.L.Gordon S.N.Christo P.Klenerman L.K.Mackay Translational Gastroenterology Unit Nuffield Department of MedicineUniversity of OxfordOxfordUK Department of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Department of Infectious Diseases Austin HealthMelbourneVICAustralia peter Medawar Building for Pathogen Research University of OxfordOxfordUK

Tissue-resident memory T(T_(RM))cells are increasingly associated with the outcomes of health and disease.T_(RM) cells can mediate local immune protection against infections and cancer,which has led to interest in T_(RM) cells as targets for vaccination and immunotherapies.However,these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis,alopecia areata,and vitiligo.Here,we summarize the biology of T_(RM) cells established in animal models and in translational human studies.We review the beneficial effects of T_(RM) cells in mediating protective responses against infection and cancer and the adverse role of T_(RM) cells in driving pathology in autoimmunity.A further understanding of the breadth and mechanisms of T_(RM) cell activity is essential for the safe design of strategies that manipulate T_(RM) cells,such that protective responses can be enhanced without unwanted tissue damage,and pathogenic T_(RM) cells can be eliminated without losing local immunity.

关键词： human T cells tissue-resident memory immunity

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Correction: Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

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Cellular & Molecular Immunology 2022年第4期19卷 554-554页

作者： Kevin Man Axel Kallies Ajithkumar Vasanthakumar peter doherty institute for infection and immunity Melbourne VIC Australia Department of Microbiology and Immunology University of Melbourne Melbourne VIC Australia Olivia Newton-John Cancer Research institute Melbourne VIC Australia

Correction to:Cellular&Molecular Immunology https://***/10.1038/s41423-021-00804-7,published online 26 November 2021 The article Resident and migratory adipose immune cells control systemic metabolism and thermogenesis,written by Kevin Man,Axel Kallies and Ajithkumar Vasanthakumar was originally published electronically on the publisher’s internet portal on 24.11.2021 without open access.

关键词： internet portal online

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