TRS THEME-BASED RESEARCH SCHEME PUBLIC SYMPOSIUM 2024 主題硏究計劃研討會 2024年12月8日(星期日) 上午10時至下午4時15分 香港科技大學 學術大樓1樓 夏利萊博士及夫人演講廳 LT-C 利榮達演講廳 LT-D The Hong Kong University of Science and Technology 1/F, Academic Building Padma and Hari Harilela Lecture Theater (LT-C) Lee Wing Tat Lecture Theater (LT-D) 8 December 2024 (Sunday) 10:00—16:15
Welcome Message from Research Grants Council 研究資助局歡迎辭 About the Theme-based Research Scheme 主題研究計劃概要 Programme 研討會程序 Project Information 項目資料 2 3 4 6 Table of Contents 目錄 6 14 20 22 THEME 主題 1 | Understanding Diseases and Disease Prevention 剖析疾病及疾病預防 A Stem Cell Approach to Dissect the Molecular Basis of Neurodegenerative Diseases 以幹細胞方法解析神經退行性疾病的分子基礎 Potentiating Host Immunity for HIV-1 Functional Cure 增強宿主免疫實現HIV-1功能性治癒 Control of In uenza: Individual and Population Immunity 流感控制：個人和群體免疫力 Fighting Disease Recurrence and Promoting Tissue Repair after Liver Transplantation: Translating Basic Discoveries to Clinical Excellence 肝移植後原發病復發和組織修復的科研攻堅：從轉化基礎研究到優化臨床決策 Sustainable Marine Infrastructure Enabled by the Innovative Use of Seawater Sea-Sand Concrete and Fibre-Reinforced Polymer Composites 基於海水海砂混凝土與纖維增強複合材料的新型可持續海洋工程結構 A Paradigm-shifting, Fully-integrated, Compact Wastewater-to-resource Facility (WWRF) 未來污水淨化與資源回收一體化工場（未來水工場） SureFire: Smart Urban Resilience and Fire ghting SureFire：智慧城市災害防控和火災應急研究 THEME 主題 2 | Developing a Sustainable Environment 建設可持續發展的環境 Contributing to the Development of Hong Kong into a Global Fintech Hub 促進香港成為全球的金融科技樞紐 THEME 主題 3 | Enhancing Hong Kong’s Strategic Position as a Regional and International Business Centre 加強香港作為地區及國際商業中心的策略地位 THEME 主題 4 | Advancing Emerging Research and Innovations Important to Hong Kong 促進對香港起重要作用的新興研究及創新項目 Image-guided Automatic Robotic Surgery 視覺導航自動機械人手術 Research and Development of Arti cial Intelligence in Extraction and Identi cation of Spoken Language Biomarkers for Screening and Monitoring of Neurocognitive Disorders 以人工智能提取和鑑定口語生物標誌物供神經認知障礙篩查和監測的研究及技術開發 1
Welcome Message from the Research Grants Council 研究資助局歡迎辭 2 The Research Grants Council (RGC) warmly welcomes you to the Theme-based Research Scheme (TRS) Public Symposium 2024. Since 2011, the TRS has been providing huge support to the academic research efforts of the University Grants Committee-funded universities on themes of strategic importance for the long-term development of Hong Kong. To date, the RGC has conducted 14 rounds of exercise, granting a total of $3.36 billion to 84 projects. Ten projects funded in the eighth and ninth rounds have been successfully completed or are approaching completion. We are delighted to have the project teams to share their achievements, novel discoveries and the impacts of their frontier research with us today, through presentations, posters display and demonstrations. Taking this opportunity, the RGC would like to express our sincere gratitude to members of the ten project teams and their universities for their contributions to making this Symposium a success. We would also like to thank the Research Office of the Hong Kong University of Science and Technology for organising the Symposium with dedication and professionalism. We look forward to seeing the positive impacts of these TRS projects on the social and economic development of Hong Kong. Research Grants Council 研究資助局 ( 研資局 ) 熱烈歡迎各位參加 2024 年主題研究計 劃研討會。 自 2011 年，主題研究計劃一直大力支持大學教育資助委員會 資助大學的學術研究力量，對香港長遠發展具策略重要性的主 題進行研究。至今研資局已舉行了 14 輪計劃，向 84 個獲資助 項目批出合共 33.6 億元撥款。在第八及第九輪獲得撥款的十 個項目已成功完成或進入最後階段。我們很高興項目團隊今天 將透過講座、海報及展覽，與我們分享他們的前沿研究成果、 嶄新發現及影響。 藉此機會，研資局衷心感謝十個項目的團隊成員和他們所屬的 大學對是次研討會的支持，使研討會得以成功舉行。我們亦感 謝香港科技大學的研發事務辧公室以充滿熱誠及專業的精神籌 辦研討會。 我們期望這些主題研究計劃項目的影響，為香港的社會和經濟 發展帶來裨益。 研究資助局
About the Theme-based Research Scheme 主題研究計劃概要 Theme 1: Understanding Diseases and Disease Prevention 1. Infectious Diseases 2. Understanding Disease Mechanisms to Improving Health 3. Stem Cells and Regenerative Medicine 4. Disease Prevention and Management Theme 2: Developing a Sustainable Environment 1. Water Pollution and Water Treatment 2. Sustainable Built Environment 3. Energy Efficiency, Conservation, Conversion and Harvesting 4. Air Quality 5. Food Production and Food Security Theme 3: Enhancing Hong Kong's Strategic Position as a Regional and International Business Centre 1. Hong Kong’s Future as an International Financial Centre 2. Promoting Hong Kong’s Business through Networking Capability 3. Promoting Hong Kong as a Centre of Excellence for Business Services 4. Innovation Ecology and Business Creation in Knowledge Economy 5. Financial Technologies (FinTech) and Regulatory Technologies (RegTech) Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong 1. Big Data and Artificial Intelligence 2. Imaging, Robotics and Smart Manufacturing 3. Urban Infrastructure and Smart City 4. Education and Digital Citizenship 5. Quantum Technology 6. Integrated Circuits The maximum duration of a project is five years. The ceiling of direct project cost per project to be awarded by the Research Grants Council is $75 million. 主題 一 剖析疾病及疾病預防 1. 傳染病 2. 剖析發病機制以保障健康 3. 幹細胞與再生醫學 4. 疾病預防與管理 主題二 建設可持續發展的環境 1. 水污染及水處理 2. 可持續建築環境 3. 能源效率、節約、轉化及採集 4. 空氣質素 5. 食物生產及食物安全 主題三 加強香港作為地區及國際商業中心的策略地位 1. 香港作為國際金融中心的未來發展 2. 通過網絡能力推動香港商業發展 3. 推廣香港成為卓越的商業中心 4. 知識經濟中的創新生態與商業創意 5. 金融科技及監管科技 主題四 促進對香港起重要作用的新興研究及創新項目 1. 大數據及人工智能 2. 造像、機械人技術及智能製造 3. 城市基礎建設及智慧城市 4. 教育及數碼公民身分 5. 量子技術 6. 集成電路 每個項目的年期最長為五年，研究資助局資助金額上限為 7 千 5 百萬元 （按直接項目成本計算）。 Theme-based Research Scheme (TRS) aims to focus academic research efforts of University Grants Committee funded universities on themes of strategic importance to the long-term development of Hong Kong. There are four designated research themes under the TRS. Under the four research themes, there are 20 grand challenge topics: 主題研究計劃的目的是集中大學教育資助委員會資助大學的學 術研究力量，對香港長遠發展具策略重要性的主題進行研究。 計劃設有四個研究主題，四個主題下共設有20個重大挑戰 題目： 3
4 Programme Opening Ceremony (Opening Speech by Chairman of Research Grants Council) Professor Timothy W. TONG, SBS, JP Registration *Theme-based Research Scheme projects showcased in Public Symposium 2024 are funded by the Research Grants Council in the Eighth Round (2018/19) and Ninth Round (2019/20) exercises. 10:00 – 10:10 9:45 – 10:00 10:10 – 10:30 10:30 – 11:15 11:15 – 11:30 11:30 – 12:15 12:15 – 13:45 Lunch Break 13:45 – 14:30 14:30 – 15:15 15:15 – 15:30 15:30 – 16:15 Presentation Sessions Poster/ Video Presentation/ Model Display Programme Time Plenary Session – Funding Mechanism of the Theme-based Research Scheme (by Chairman of Collaborative Research Projects Steering Committee) Professor Paul KL YU Venue: LT-C Venue: LT-D Theme 1 - Understanding Diseases and Disease Prevention THEME 1 (A1) A Stem Cell Approach to Dissect the Molecular Basis of Neurodegenerative Diseases Professor Nancy IP (to be presented by the Deputy Project Coordinator, Professor Zhenguo WU) The Hong Kong University of Science and Technology THEME 1 (A2) Potentiating Host Immunity for HIV-1 Functional Cure Professor Zhiwei CHEN The University of Hong Kong THEME 1 (A3) Control of Influenza: Individual and Population Immunity Professor Benjamin John COWLING The University of Hong Kong THEME 1 (A4) Fighting Disease Recurrence and Promoting Tissue Repair after Liver Transplantation: Translating Basic Discoveries to Clinical Excellence Professor Nancy Kwan MAN The University of Hong Kong Poster and video presentations, as well as model displays (if any), from the 10 project teams are showcased outside LT-C and LT-D. Theme 3 - Enhancing Hong Kong’s Strategic Position as a Regional and International Business Centre THEME 3 (A5) Contributing to the Development of Hong Kong into a Global Fintech Hub Professor Kar Yan TAM The Hong Kong University of Science and Technology Theme 4 - Advancing Emerging Research and Innovations Important to Hong Kong THEME 4 (B4) Image-guided Automatic Robotic Surgery Professor Yunhui LIU The Chinese University of Hong Kong THEME 4 (B5) Research and Development of Artificial Intelligence in Extraction and Identification of Spoken Language Biomarkers for Screening and Monitoring of Neurocognitive Disorders Professor Helen MENG The Chinese University of Hong Kong THEME 2 (B3) SureFire: Smart Urban Resilience and Firefighting Professor Asif Sohail USMANI The Hong Kong Polytechnic University THEME 2 (B2) A Paradigm-shifting, Fully-integrated, Compact Wastewater-to-resource Facility (WWRF) Professor Guanghao CHEN The Hong Kong University of Science and Technology Theme 2 - Developing a Sustainable Environment THEME 2 (B1) Sustainable Marine Infrastructure Enabled by the Innovative Use of Seawater Sea-Sand Concrete and Fibre-Reinforced Polymer Composites Professor Tao YU The Hong Kong Polytechnic University Tea Break Tea Break
5 研討會程序 專題演講 時間 研討會程序 開幕致詞: 研究資助局主席 唐偉章教授, SBS, JP 主題研究計劃撥款機制簡介: 協作研究項目督導委員會主席 余刼離教授 地點: 演講廳 LT-C 地點: 演講廳 LT-D 主題一 剖析疾病及疾病預防 主題一 (A1) 以幹細胞方法解析神經退行性疾病的分子基礎 葉玉如教授 (由副項目統籌人鄔振國教授代爲演講) 香港科技大學 主題一 (A2) 增強宿主免疫實現HIV-1功能性治癒 陳志偉教授 香港大學 主題一 (A3) 流感控制：個人和群體免疫力 高本恩教授 香港大學 主題二 (B3) SureFire: 智慧城市災害防控和火災應急研究 Asif Sohail USMANI教授 香港理工大學 主題一 (A4) 肝移植後原發病復發和組織修復的科研攻堅：從轉化 基礎研究到優化臨床決策 萬鈞教授 香港大學 主題四 促進對香港起重要作用的新興研究及 創新項目 主題四 (B4) 視覺導航自動機械人手術 劉雲輝教授 香港中文大學 主題三 加強香港作為地區及國際商業中心的策略地位 主題三 (A5) 促進香港成為全球的金融科技樞紐 譚嘉因教授 香港科技大學 主題四 (B5) 以人工智能提取和鑑定口語生物標誌物供神經認知障 礙篩查和監測的研究及技術開發 蒙美玲教授 香港中文大學 主題二 (B2) 未來污水淨化與資源回收一體化工場 (未來水工場） 陳光浩教授 香港科技大學 主題二 建設可持續發展的環境 主題二 (B1) 基於海水海砂混凝土與纖維增強複合材料的新型可持 續海洋工程結構 余濤教授 香港理工大學 茶 歇 茶 歇 午 膳 有關十個項目的海報展覽、介紹影片及模型 (如有) 於LT-C 及LT-D外展示。 *本研討會所有研究項目均為研究資助局在第八輪 (2018/19年度) 和第九輪 (2019/20年度) 主題研究計劃撥款資助的項目。 海報展覽、介紹影片及模型展示 登記 9:45 – 10:00 10:00 – 10:10 10:10 – 10:30 10:30 – 11:15 11:15 – 11:30 11:30 – 12:15 12:15 – 13:45 13:45 – 14:30 14:30 – 15:15 15:15 – 15:30 15:30 – 16:15
Short Biography of Project Coordinator Professor Nancy Ip received her PhD degree in Pharmacology from Harvard University, after which she held the position of Senior Staff Scientist at Regeneron Pharmaceuticals Inc. in New York. Professor Ip joined HKUST in 1993 and is currently The Morningside Professor of Life Science and Chair Professor in the Division of Life Science. She is internationally renowned for her significant contributions to the field of neuroscience, particularly in understanding the complex mechanisms that underlie proper brain functions and in drug discovery for neurodegenerative diseases. Her outstanding research has resulted in more than 330 scientific papers and over 70 patents. She was elected as Fellows of the Chinese Academy of Sciences, the US National Academy of Sciences, and the American Academy of Arts and Sciences, among other academies, and is a recipient of numerous awards and honors, including the National Natural Science Awards and the L’OREAL-UNESCO for Women in Science Award. Project Summary Mission: Address the urgent need for new and innovative therapies that can treat age-related neurodegenerative disorders. Goal: Use human induced pluripotent stem cell (iPSC) and genome-editing technologies to investigate the pathological mechanism of Alzheimer's disease (AD). Objectives: • Establish a human iPSC core for in vitro modeling and functional studies. • Examine how genetic variants contribute to AD. • Perform drug screening and preclinical drug development using iPSC-derived platforms and established animal models. Deliverables: • Identify and elucidate the molecular pathways that contribute to AD pathogenesis. • Use genome-editing technologies to introduce or correct specific mutations in iPSCs. • Identify potential molecular targets for therapeutic intervention of AD. 項目概要 使命： 聚焦老齡相關的神經退行性疾病，探尋創新療法以應 對迫切需求。 目標： 利用人源誘導多能幹細胞（iPSC）和基因編輯技 術，研究阿茲海默症 (AD) 的病理機制。 目的： • 建立人源 iPSC 核心平臺，進行體外建模和功能研究。 • 研究遺傳變異如何導致 AD。 • 使用 iPSC 衍生平臺和動物模型進行藥物篩選和臨床 前藥物開發。 成果： • 辨識及闡明 AD 致病機制的分子途徑。 • 利用基因組編輯技術引入或修正 iPSC 中的特定突變。 • 辨識治療 AD 的潛在分子靶點。 項目統籌人簡介 葉玉如教授於美國哈佛大學獲藥理學博士學位，其後在紐約 Regeneron 製藥公司擔任高級科學家。她於 1993 年起受聘於 科大，現任晨興生命科學教授及生命科學部講座教授。葉教授 是國際知名學者，在解析大腦功能的複雜機制以及研發神經退 化性疾病新藥方面有重大貢獻，發表了超過 330 篇論文和綜 述，擁有 70 多項科技發明專利。葉教授還當選為多間學術機 構的院士，包括中國科學院、美國國家科學院、美國人文與 科學院，並獲頒多個國內外重要學術獎項，包括國家自然科學 獎、歐萊雅聯合國教科文組織「世界傑出女科學家成就獎」。 The level of amyloid plaque deposition (white shades in area encircled by green dotted lines), a pathological hallmark of AD, is high in the brain of AD mouse (left) and decreases after the application of the genome editing therapy throughout the brain (right). AD小鼠大腦（左圖）中有大量澱粉樣斑塊沉積，這是AD最主要的 病理性標誌物（綠色虛線區域中的白色陰影）。經過基因編輯治療 後，白色陰影明顯下降（右圖）。 6 A Stem Cell Approach to Dissect the Molecular Basis of Neurodegenerative Diseases 以幹細胞方法解析神經退行性疾病的分子基礎 T13-605/18-W Project Coordinator Professor Nancy IP The Hong Kong University of Science and Technology 項目統籌人 葉玉如教授 香港科技大學 THEME 主題 1 | Understanding Diseases and Disease Prevention 剖析疾病及疾病預防 Participating Institutions City University of Hong Kong The Chinese University of Hong Kong The University of Hong Kong 參與院校 香港城市大學 香港中文大學 香港大學
Research Impact We have succeeded in developing advanced capabilities and generating valuable data towards establishing groundwork to develop novel therapies to treat incurable neurological diseases, such as AD, and hence addressing critical unmet medical needs and easing the associated financial burdens. In the long run, these newly established advanced capabilities and technologies will drive research excellence at local institutions, increase collaborations with mainland China and international institutes, provide training opportunities for young scientists, place Hong Kong on the map for advanced neural regenerative medicine and stem cell research, and will ultimately strengthen Hong Kong's position as an international innovation and technology centre. 研究影響 我們擁有先進的研究能力並取得重要數據，為治理 AD 等無法 治癒的神經系統疾病提供了理論基礎，有助應對醫療需求缺口 及減輕相關的經濟重擔。長遠而言，這些先進的科研能力和技 術將有助推動本港卓越研究，加強與內地和國際機構的合作， 為年輕科學家提供培訓機會，讓香港在先進神經再生醫學和幹 細胞研究領域居前，鞏固香港作為國際創新科技中心的地位。 Abstract This project represents our continuing effort to address the urgent need for new and innovative therapies that can treat age-related neurodegenerative disorders, such as the highly prevalent and devastating AD. We have established the capability and platforms for iPSC differentiation into specific brain cell types and brain organoids. The current project builds upon these findings and further explores the pathological mechanism of AD using innovative approaches that harness advanced stem cell and genome-editing technologies. With these technologies, we have succeeded in generating and utilizing patient-derived iPSCs that carry genetic risk variants for AD to conduct detailed investigations on the disease pathophysiology. The establishment of the iPSC-derived neuronal platform provides a useful tool to evaluate the efficacy and safety of drug candidates on human neurons. Furthermore, we have developed a novel strategy using brain-wide genome-editing technology that can reduce AD pathologies in genetically modified AD mouse models. This advanced technology has garnered significant attention and awards, including the 2021 "Major Breakthrough in Neuroscience" award from the Chinese Neuroscience Society and a Gold Medal at the 49th International Exhibition of Inventions Geneva, for its potential to be translated into a novel long-acting therapeutic treatment for AD patients. It is among the first selected for the “Research, Academic, and Industry Sectors One-plus (RAISe+) Scheme” by the Innovation and Technology Commission of the HKSAR Government. 項目簡介 我們持續努力探尋創新療法應對與老齡相關的神經退化性疾 病，例如嚴重威脅人們健康的高發病 AD，以滿足迫切的需要。 我們建立了平臺，能將 iPSC 分化成特定腦細胞類型和產生腦 類器官。本項目在此基礎上，利用先進的幹細胞和基因組編輯 技術進一步探索 AD 的病理機制。我們建立了源自攜帶 AD 遺 傳風險變異患者的 iPSC，藉此深入研究病理生理學。這些 iPSC 衍生的神經元，亦可用作評估候選藥物的功效和安全性。 此外，我們成功研發出一種新型全腦基因編輯技術，在小鼠模 型中證明可以改善 AD 的病理症狀，有潛力發展成爲 AD 的新 型長效治療手段。該技術獲得了中國神經科學學會 2021 年度 「神經科學重大進展」殊榮，在第四十九屆日內瓦國際發明展 上取得金獎，並成為首批獲創新科技署「產學研 1+ 計劃」 （RAISe+）資助的項目之一。 First Members’ Meeting held on 12 Dec 2018 首次會員大會於2018年12月12日召開 Fourth Annual Symposium held on 09 Jan 2024 第四屆年度研討會於2024年1月9日舉行 7
Short Biography of Project Coordinator Professor Zhiwei Chen is an expert in the field of HIV/AIDS and emerging infectious diseases. He is an inventor/co-inventor of two AIDS and two COVID-19 vaccines, which have been developed from the laboratory to human phase I trials in the Mainland and Hong Kong. His invention of PD1-based DNA vaccines and bi-specific antibodies against HIV/AIDS serves the core of this project. Prof Chen has obtained many grants, including TRS, the General Research Fund, the Collaborative Research Fund, and Health and Medical Research Fund in Hong Kong, as well as international fundings from National Institutes of Health and the Bill & Melinda Gates Foundation. With his coordination, the research team generates consistently high-impact research outputs and promotes the technology transfer of the “made in Hong Kong” immunotherapeutic products for clinical development. Project Summary To determine correlates of PD1-based vaccine and BiIA-SG- induced protection in SHIVSF162P3CN-infected rhesus macaques. To determine immunogenicity and efficacy of GLP-grade human PD1-based vaccine and BiIA-SG in animal models in support of Investigational new drug (IND) application. To investigate the possible functional cure of HIV-1 infection in patients by PD1-based vaccine and BiIA-SG immunotherapies. 項目概要 研究 PD-1 增強型 DNA 疫苗和雙特異性抗體在 SHIV SF162P3CN 感染的恒河猴中誘導的保護效力。 研究 GLP 級別生產的人 PD-1 增強型 DNA 疫苗和雙特異性抗體 在動物模型中的免疫原性和功效，以支持新藥臨床試驗 ( IND) 申請 。 探討 PD-1 增強型 DNA 疫苗和雙特異性抗體免疫療法對 HIV-1 感染者功能性治癒的可能性。 項目統籌人簡介 陳志偉教授是愛滋病和新興傳染病領域的專家。他是兩種愛滋 病疫苗和兩種新冠肺炎疫苗的發明者 / 共同發明者。目前，這 些疫苗均已在內地和香港從實驗室研發階段進階至 I 期臨床試 驗階段。陳教授團隊研發的 PD-1 增強型 DNA 疫苗和雙特異 性抗體是此項目的核心關鍵。陳教授獲得了多項研究基金的資 助，包括香港的主題研究計劃、優配研究金、協作研究金和 醫 療衞生研究金項目，以及來自美國國立衞生研究院和比爾及梅 琳達蓋茲基金會的海外資助。在他的統籌下，研究團隊不僅持 續產出高影響力的研究成果，並促進「香港製造」免疫療法候 選藥物的技術轉移以應用於臨床。 Professor Kwok-Yung Yuen visiting ICVAX clinical trial onsite 袁國勇教授現場考察指導ICVAX臨床研究 The research team working in Laboratory 在實驗室工作的研究團隊 8 Potentiating Host Immunity for HIV-1 Functional Cure 增強宿主免疫實現HIV-1功能性治癒 T11-706/18-N Project Coordinator Professor Zhiwei CHEN The University of Hong Kong 項目統籌人 陳志偉教授 香港大學 Participating Institution The Chinese University of Hong Kong 參與院校 香港中文大學 THEME 主題 1 | Understanding Diseases and Disease Prevention 剖析疾病及疾病預防
Research Impact Our overall objective is to potentiate host immunity to achieve a functional cure for HIV-1 infection, a status of suppressed viremia below the limit of detection, for benefiting PLWH without receiving ART. First, our research team successfully brought the ICVAX vaccine into Phase I clinical trial and illustrated the translational process and the underlying mechanisms of our scientific discoveries into clinical development step by step. It leads to a promising “made in Hong Kong” immunotherapeutic candidate for the functional cure of AIDS. Second, by establishing a Hong Kong consortium of outstanding scientists and biomedical R&D companies, we generated GLP/GMP-grade vaccines or antibodies for preclinical and clinical studies. We also developed the PD-1-based vaccination platform not only in the field of HIV/AIDS, but also in other diseases such as COVID-19 and cancer with 2 patents granted and 1 patent filed. Third, we generated 20 peer-reviewed publications in leading scientific journals and 17 international conference papers during this project period. Moreover, we have obtained research grants from other sources to work on 4 new projects, which evolved directly from this TRS project. These projects further promote our future biomedical research and drug development in the area of infectious diseases. 研究影響 研究團隊的整體目標是透過增強宿主免疫以實現愛滋病病毒感 染者（PLWH）的功能性治癒，從而使 PLWH 在不接受 ART 的情況下實現病毒血症抑制至檢測限以下的狀態。首先，研 究團隊已成功地將 ICVAX 疫苗推進至 I 期臨床試驗，並展現了 我們將科學發現逐步轉化至臨床試驗的過程及相關機制。此 「香港製造」免疫治療候選藥物有望在未來用於愛滋病功能性 治癒。其次，透過成立一個由傑出科學家和生物醫藥研發公司 組成的香港聯盟，研究團隊成功生產了 GLP/GMP 級疫苗或抗 體並進行了臨床前及臨床研究。團隊亦在多領域開發了 PD-1 增強型 DNA 疫苗。愛滋病領域以外，該疫苗也用於其他疾病 領域，例如 COVID-19 和癌症，並取得兩項獲批的專利和一項 受審批中的專利。第三，在此項 TRS 期間，我們在前沿科學期 刊上發表了 20 篇科研論文，並在多個國際會議上發表了 17 份 報告。另外，研究團隊受此項 TRS 啟發，亦成功獲批 4 項其他 研究基金，這些科學研究亦將進一步加強研究團隊未來在傳染 病領域的生物醫學基礎研究和藥物研發。 Abstract HIV/AIDS has been a major health burden worldwide, with more than 39.0 million people living with HIV-1 (PLWH) currently. In Hong Kong, there are more than 11943 accumulative cases reported in total nowadays. Although combined anti-retroviral therapy (cART) is available, this life-long treatment is expensive and may cause adverse effects or drug resistance in PLWH. This TRS project aims to develop a promising immunotherapeutic strategy to suppress HIV-1 infection to undetectable viremia levels in PLWH without life-long cART. Our research team has set up collaborations with two biomedical companies for the manufacture of Good Laboratory Practice/ Good Manufacturing Practice (GLP/GMP)-graded PD-1-based DNA vaccine (ICVAX vaccine) and bi-specific antibody (BiIA-SG). The preventive or protective efficacies against AIDS, as well as their underlying mechanisms, were tested in the SHIV-infected rhesus macaque model. Collectively, both immunotherapeutic strategies work efficiently and effectively in prophylactic administration at the pre-exposure and/or post-exposure of viral infection. After obtaining various approvals of GMP, IND, research ethics, etc., we successfully brought the ICVAX vaccine into Phase I clinical trial. Our 5-year TRS project illustrated the translational process of our scientific discoveries into clinical development. It leads a promising “made in Hong Kong” immunotherapeutic candidate to the future hope of local and international AIDS communities. 項目簡介 愛滋病是全球公共健康的主要難題之一，目前有超過 3,900 萬 愛滋病病毒感染者（PLWH）。香港目前累計報告個案超過 11943 例。儘管 PLWH 可以使用聯合抗逆轉錄病毒療法 （cART），但這種終生治療價格昂貴，並且可能導致 PLWH 產 生不良反應或抗藥性。此 TRS 項目旨在研發一種有前景的免疫 治療策略，將 PLWH 的病毒感染抑制至不可檢測的病毒血症 水平，並且無需終身服用 cART。 研究團隊與兩家生物醫藥公司建立合作，生產 GLP/GMP 級別 的 PD-1 增強型 DNA 疫苗（ICVAX 疫苗）和雙特異性抗體 （BiIA-SG），在感染 SHIV 的恒河猴模型中檢測了兩者對愛滋 病的預防或保護效力及其相關機制。總體而言，兩種免疫治療 策略在病毒感染暴露前和 / 或暴露後的預防性給藥中均有效且 效果顯著。在獲得 GMP、IND、科研倫理等多個委員會核准 後，我們最終成功將 ICVAX 疫苗推進至 I 期臨床試驗。此項為 期 5 年的 TRS 項目也展示出我們將科學發現轉化至臨床試驗的 過程。ICVAX 疫苗未來有望成為「香港製造」的免疫治療候選 藥物，為本地和國際愛滋病病人帶來希望。 The photo of the project team 此項目的團隊合照 9
International Conference on Individual and Population Immunity to Respiratory Viruses, held on November 8-10, 2023 2023 年 11 月 8 至 10 日舉行了以「個人和群體對呼吸道病毒的免疫力」為題的國際性會議 Short Biography of Project Coordinator Professor Ben Cowling is currently Chair Professor of Epidemiology, Head of the Division of Epidemiology and Biostatistics and Helen and Francis Zimmern Professorship in Population Health in the School of Public Health at the University of Hong Kong, and co-Director of the WHO Collaborating Centre for Infectious Disease Epidemiology and Control. He conducts research on the epidemiology and control of respiratory infections, particularly respiratory virus infections including COVID-19 and influenza. He’s a Clarivate Web of Science “Highly Cited Researcher” since 2021 and among the “top 1% most cited scientists” since 2014. Project Summary Influenza causes more health impact than any other infectious disease in Hong Kong, each year, prior to the COVID-19 pandemic. Influenza vaccines are the most used seasonal vaccines in the world (more than 500 million doses administered worldwide each year, more than 1 million in Hong Kong), but their effectiveness is not as good as we would like in some years. This funded project has been studying human immunity to influenza with the aim of improving our scientific knowledge, enhancing efficiency of vaccines, and more generally reducing the health impact of influenza in Hong Kong each year. We redirected efforts towards COVID-19 research in the first two years of the pandemic, making important contributions to evidence-based policies to reduce the impact of the pandemic. 項目概要 在 2019 冠狀病毒病（COVID-19）大流行之前，流感相對其 他傳染病，每年對香港公眾的健康問題影響較大。 流感疫苗是世界上最常用的季節性疫苗（全球每年使用劑量 超過 5 億劑，香港超過 100 萬劑），但有時候其抗病效果不似 預期。 此資助項目研究人類對流感的免疫力，加強我們的科學知識， 提升疫苗有效性，以減低流感每年對香港公眾健康問題的影 響。 首兩年此項目重點轉為 2019 冠狀病毒病大流行研究，為減少 大流行影響的實證政策作出了重要貢獻。 項目統籌人簡介 高本恩現為香港大學公共衞生學院的流行病學講座教授、流 行病和生物統計學分部主任及施玉榮伉儷基金教授席 ( 民眾健 康 )，同時擔任世界衞生組織傳染病流行病學及控制合作中心 聯席總監。高教授從事有關呼吸道感染流行病學及控制的學術 研究，特別是 2019 冠狀病毒病和流感等呼吸道病毒感染。 2021年起他入選科睿唯安「最廣獲徵引研究人員」，2014 年起 躋身「獲徵引次數位於前 1% 的科學家」。 10 Control of In uenza: Individual and Population Immunity 流感控制：個人和群體免疫力 T11-712/19-N Project Coordinator Professor Benjamin John COWLING The University of Hong Kong 項目統籌人 高本恩教授 香港大學 Participating Institutions The Chinese University of Hong Kong The University of Melbourne 參與院校 香港中文大學 墨爾本大學 THEME 主題 1 | Understanding Diseases and Disease Prevention 剖析疾病及疾病預防
Photo of Project Team and Scientific Advisory Board 研究團隊與科學諮詢委員會留影 Research Impact Our research program has produced important and high-impact scientific findings on individual and population immunity to influenza, and made essential contributions to evidence-based policy making during the COVID-19 pandemic. Our multidisciplinary influenza research group is recognised as world-leading, and demonstrated our value to Hong Kong SAR, greater China, and the world during the COVID-19 pandemic where we published a large number of top-tier publications, advised local, national and international health agencies, and frequently communicated our knowledge and recommendations to the public via traditional and social media. 研究影響 我們的研究計劃在個人和群體的流感免疫力方面取得了重要且 具有很高影響力的科學成果，並在 2019 冠狀病毒病大流行期 間為實證政策作出了重要貢獻。我們的跨學科流感研究團隊獲 認可為全球領先，在 2019 冠狀病毒病大流行期間，我們發表 了大量頂尖論文，為本地、國家和國際衞生機構提供意見，並 通過傳統和社交媒體頻繁地向公眾傳播知識和提供建議，向香 港特別行政區、大中華地區及世界展示了我們的價值。 Abstract Influenza is a major threat to global public health. Seasonal influenza viruses cause annual epidemics with significant morbidity and mortality but existing vaccines are not optimal. Our own studies have shown that hemagglutination inhibition antibody titers, which are the current correlate of protection against influenza, only explain around 57% of the protective effect of conventional inactivated vaccines. These antibodies are even less correlated with the protection provided by live attenuated influenza vaccines or new vaccines currently in development. Therefore, key knowledge gaps addressed in this project: (a) what are the immune correlates of protection against influenza infection or severe disease; (b) which of these are induced temporarily or permanently by prior natural infection or different types of vaccination; (c) what are the factors which contribute to increased susceptibility of populations to influenza epidemics; (d) how should we best deploy new and existing influenza vaccines to reduce the impact of influenza epidemics and pandemics; and (e) what are other immunological mechanisms relevant to the development and evaluation of new influenza vaccines. The relevance of these and other previously undefined mechanisms for protection against infection and disease in humans is the major knowledge gap. 項目簡介 流行性感冒嚴重威脅全球公共衞生。季節性流感病毒能導致每 年流感大流行及引發顯著的發病和死亡率，但現有的流感疫苗 並非最佳的抗病疫苗。我們過往的研究發現，血球凝集抑制抗 體滴度（目前已知具有防護流感感染的抗體滴度）僅能解釋常 規滅活疫苗約 57％的保護作用。這些抗體較目前正在研發的減 活或新型流感疫苗所提供的保護性更低。 因此，此項目關鍵的知識差距為：（一）什麼是預防感染或嚴 重疾病的免疫相關保護因子 ;（二）哪些免疫相關保護因子屬 暫時或永久性，並源自先前的自然感染或不同類型的疫苗接 種 ;（三）什麼因素導致人類群體對於流感有更高的易感性 ; （四）如何有效地配給嶄新和現有的流感疫苗，以減輕流感大 流行和流行病的影響 ;（五）了解免疫機制以開發和評估下一 代新型流感疫苗。此研究項目有助了解上述領域和其他未釐定 的人類病毒感染之後宿主的免疫機制。 11
12 Short Biography of Project Coordinator Nancy Kwan Man, MBBS, MS, PhD, is the Chair Professor of Transplant Oncology and Immunology in Department of Surgery, The University of Hong Kong. She is the Director of Clinical and Translational Research Laboratory, Director of Liver Transplantation and Liver Cancer Research, and Director of the Laboratory for Organ Transplantation and Regeneration. She is also the President of Hong Kong Society for Immunology, and President of Hong Kong Scientist Association. Dedicated to enhancing the outcomes of liver transplantation through reducing graft injury and cancer recurrence, Nancy leads research endeavours encompassing basic, clinical, and translational studies resulting in major advances on transplant oncology and immunology in the world. As the top 2% Scientists Worldwide on Stanford List, Nancy has published more than 210 papers in leading international journals with 17000 citations (H index 74). She and her team received numerous international awards including Basic Science Established Investigator Award and Rising Star Awards from International Liver Transplantation Society (ILTS), and Mentor/Mentee Awards from The Transplantation Society (TTS). Project Summary To understand the role of regional specialization of immune system in tumor recurrence and hepatitis B after liver transplantation by the approach of systems biology integrated with a series of clinical, basic and translational studies. The new concept of immunotherapies will be developed by educating the intragraft immune micro-environment to prevent tumor recurrence after liver transplantation and to achieve the long-term survival. To establish a new modeling system that integrates high-throughput sequencing data and biology/immunology parameters not only for predicting disease recurrence and prognoses, but also for therapeutic guidance. To explore the mechanism of marginal liver graft injury and to establish novel therapeutics to overcome graft injury by using bioengineered cells targeted for regional tissue repair and functional regeneration. 項目概要 通過一系列基礎、臨床與轉化研究來揭示肝移植後原發病復 發的機制，尋找有效的生物標記物，並開發新的免疫治療方 案，從而減少移植後乙肝和肝癌的復發，提高肝移植病人的長 期生存率。 整合高通量基因測序及生化和免疫數據，建立一個嶄新的智 能模型，不僅能用於腫瘤復發的預測，亦對治療策略的選擇 具有重要的指導意義。 探索促進肝組織修復和再生的新策略，為進一步擴大供體來源 和避免移植肝損傷及失功能提供理論依據和新的治療方案。 項目統籌人簡介 萬鈞教授現任香港大學外科學系講座教授（移植腫瘤學及免疫 學 )，香港大學外科學系臨床與轉化實驗室主任，器官移植與 再生實驗室主任，肝移植與肝癌實驗室主任。主要從事肝臟移 植損傷，肝癌及其肝移植後腫瘤復發的臨床，轉化和基礎研 究，提出移植腫瘤學與免疫學的新概念。發現並闡明小體積移 植肝損傷及肝移植後肝癌復發的新機轉。研究成果處於相關領 域的國際領先水平，並在多家國際知名期刊上發表了超過 210 篇論文，其中包括：Journal of Hepatology, Gastroenterology, Annals of Surgery, Transplantation, Liver Transplantation, Clinical Cancer Research and Cancer Research, New England Journal of Medicine, Nature Medicine 等。引 用 次 數 超 過 17000 次 (H index 74)。2013-2019 年起連續七年被評為港大 最高（1%）引用率學者，她是史丹福大學 2023 全球前 2% 頂 尖科學家。近 16 年來萬鈞教授帶領的研究團隊在肝臟移植， 肝癌和肝炎的研究領域獲得超過 65 項國際大獎。 Fighting Disease Recurrence and Promoting Tissue Repair after Liver Transplantation: Translating Basic Discoveries to Clinical Excellence 肝移植後原發病復發和組織修復的科研攻堅： 從轉化基礎研究到優化臨床決策 T12-703/19-R Project Coordinator Professor Nancy Kwan MAN The University of Hong Kong 項目統籌人 萬鈞教授 香港大學 Participating Institution The Chinese University of Hong Kong 參與院校 香港中文大學 THEME 主題 1 | Understanding Diseases and Disease Prevention 剖析疾病及疾病預防
13 Project Coordinator and her team 項目統籌人及團隊 Research Impact We will address the key issues of disease recurrence after liver transplantation through exploring the underlying mechanisms, identifying efficacious biomarkers, and developing new concept targeting immunotherapies as well as precise stem cell treatments through the integration of basic, translational and clinical research. The proposed study will not only generate scientific publications and patents, but also provide many opportunities to train future research talents. In addition to bibliometric output and education, we will also develop a unique computer modeling system essential for both disease prognoses and therapeutic guidance. Such novel digitalized platform and database will be durably important to form the infrastructure for precision medicine in transplantation. Discovery of druggable targets and exploration of new therapeutic strategies targeting disease recurrence after transplantation will open a new window for collaboration with local industries to enhance technology transfer. Development of novel immunotherapy will benefit the recipients’ long-term outcomes with both societal and economic impact. 研究影響 我們研究團隊針對肝移植後原發病復發的臨床問題和科學問 題，將進行一系列綜合性的基礎、轉化和臨床研究，冀在乙肝復 發的新型免疫治療、移植肝損傷研究的新理論、腫瘤復發機理 的全新闡釋和原發病復發的治療新策略等方面取得突破性進展 和新發現，這對於指導臨床決策和夯實肝移植後原發病復發的 理論基礎具有奠定性的重要作用。系列研究也將闡明肝移植術後 原發病復發的關鍵機制及調控途徑，不僅能豐富移植免疫與腫 瘤免疫新理論，亦為個體化預防原發病復發和改進免疫調控方 案提供理論依據和技術支撐，為香港地區乃至全國和全球的乙肝 與肝癌防治提供最優化解決方案。研究團隊也將和本地醫藥企 業進行協作研發，為進一步開展臨床試驗打下良好的基礎，開發 更具成本效益的新型免疫治療將創造更好的社會與經濟效益。 Abstract During the past two decades, we have successfully built an internationally renowned liver transplantation centre in Hong Kong. We pioneered in living donor liver transplantation (LDLT) using the right lobe liver graft in the world. This surgical innovation has successfully rescued almost 1500 patients with end-stage liver diseases and liver cancer in this sole transplantation center of Hong Kong. However, the prevalence of hepatitis B virus (HBV) infection, high incidence of liver cancer (Hepatocellular carcinoma-HCC) and the shortage of deceased organ donors in Hong Kong has burdened heavily on the healthcare systems. We face the grand challenges of recurrent diseases and liver graft injury after transplantation. Our TRS aims to improve the long-term outcomes of liver transplantation by tackling two major recurring diseases including cancer recurrence and HBV reactivation in Hong Kong through exploring underlying mechanisms, identifying efficacious biomarkers, and developing potential treatments by integrating basic, translational and clinical research. We hypothesize that novel approaches promoting liver tissue repair and regeneration will abrogate the limit of donor organ shortage. We have established a Biobank with comprehensive clinical database for more than 20 years with around 50000 tissue and liquid biopsies from almost 1400 adult recipients with 100% of patient follow-up. Based on this Biobank, we will establish a modeling system that integrates high-throughput sequencing data and biology/immunology parameters not only for predicting disease recurrence and prognoses, but also for therapeutic guidance. We will develop cost-effective immunotherapies as novel prophylaxis, especially for the pre-treatment of living donors, to benefit the recipients’ long-term outcomes with both societal and economic impact. The proposed multidisciplinary collaborative project will not only strengthen our local and regional excellence, but also enhance Hong Kong as an internationally leading centre of excellence in liver transplant. In addition to patient and economic benefits, this project will cement Hong Kong’s international stature in science, medicine and education. 項目簡介 在過去的二十多年，我們成功建立了蜚聲國際的香港大學瑪麗 醫院肝臟移植中心，在全球率先開展了成人右半肝活體肝移 植。這項外科技術的創新挽救了香港地區近一千五百位患有終 末期肝病和肝癌的病人。目前，香港地區乙型病毒性肝炎和肝 癌的高發病率給本地醫療保健系統帶來沉重的負擔，肝移植後 發生的移植肝損傷和原發病包括乙肝和肝癌的復發也是我們面 臨的巨大挑戰，這更使香港醫療保健系統百上加斤。我們的研 究專案旨在通過一系列基礎、臨床與轉化研究來揭示肝移植後 原發病復發的機制，尋找有效的生物標誌物，並開發新的治療 方案，以減少移植後乙肝和肝癌的復發，提高肝移植病人的長 期生存率。為解決腦死亡供體匱乏的問題，我們也致力於探索 促進邊緣性供肝組織修復和再生的新策略。我們的肝移植中心 已建立了逾二十年的生物樣本庫與病人資料庫，其中包括近一 千四百位肝移植病人的組織和血樣本五萬多個，病人的隨訪率 達到百分之百。基於這個完善的生物樣本庫與病人資料庫，我 們將整合高通量基因測序及生化和免疫資料，建立一個嶄新的 智能模型，不僅能用於腫瘤復發的預測，而且對治療策略的選 擇也有重要的指導意義。我們也將開發新型免疫治療以改善病 人預後，在擴大病人獲益的同時創造更好的社會與經濟效益。 此項多學科合作研究不僅能鞏固我們肝臟移植中心在亞太地區 的領導地位，而且可以進一步強化我們在國際移植界，特別是 活體肝移植領域的領先優勢，亦更有利於提升香港在科學、醫 療和教育的國際地位。
The 7th FRP-SSC Workshop 第七屆FRP-SSC國際研討會 Short Biography of Project Coordinator Professor Tao YU is a Professor in Structural Engineering in the Department of Civil and Environmental Engineering and an Associate Director of the Research Institute for Sustainable Urban Development at The Hong Kong Polytechnic University. Professor YU’s research focuses on infrastructure applications of composite materials, with emphasis on innovative hybrid structures enabled by fibre-reinforced polymer (FRP) and FRP-seawater sea-sand concrete (SSC) structures. Professor YU has authored or co-authored over 160 research papers, which have received over 9000 citations. Professor YU is one of the main contributors for the Chinese national standard “Technical Standard for FRP in Construction (GB50608-2020)” and an inventor of several novel high-performance structural elements incorporating FRP. Professor YU received many prestigious awards, including the Distinguished Young Researcher Award from the International Institute for FRP in Construction (IIFC), and the 2018 Golden Wattle Award (Top Ten Outstanding Australian Chinese Youth). 項目統籌人簡介 余濤教授現任香港理工大學土木及環境工程學系結構工程教授 及可持續城市發展研究院副院長，主要研究領域為土木工程複 合材料結構，包括新型複材組合結構及複材 - 海水海砂混凝土 結構，發表學術論文 160 餘篇，論文被引 9000 餘次。余濤教 授是國家標準《纖維增強複合材料建設工程應用技術規範 - GB50608》的主要起草人之一，也發明了多種新型高性能複材 組合構件，曾獲國際土木工程複合材料學會傑出青年學者獎、 澳大利亞十大傑出華人青年金合歡獎等獎項。 Project Summary The fundamental mechanisms of seawater sea-sand concrete (SSC) have been clarified, and various types of SSC have been developed through mix proportion optimisation. Various innovative forms of FRP-SSC structural members and connections have been developed, and reliable design methods have been established for them. Various types of sensors, including pH, moisture, chloride, sulphate sensors, have been developed and integrated into a sensing system for hybrid monitoring of the long-term performance of FRP-SSC structures. A performance simulation platform based on multi-scale multi-physics modelling of deterioration at the material and structure levels and the accelerated and field exposure tests has been established for predicting the long-term performance of FRP-SSC structures. 項目概要 闡明海水海砂混凝土（SSC）的基本機理，並在此基礎上通過 配合比優化研發多種類型的 SSC。 研發多種新型 FRP-SSC 結構構件和連接，並為其建立可靠的 設計方法。 研發多種類型的傳感器，包括 pH、濕度、氯離子和硫酸根離 子傳感器，並將其集成到傳感系統中，用於混合監測 FRP-SSC 結構的長期性能。 基於材料和結構層面劣化的多尺度、多物理場模擬以及加速和 現場暴露試驗的結果，建立一個性能模擬平臺，用於預測 FRP-SSC 結構的長期性能。 Sustainable Marine Infrastructure Enabled by the Innovative Use of Seawater Sea-Sand Concrete and Fibre-Reinforced Polymer Composites 基於海水海砂混凝土與纖維增強複合材料的 新型可持續海洋工程結構 T22-502/18-R Project Coordinator Professor Tao YU The Hong Kong Polytechnic University 項目統籌人 余濤教授 香港理工大學 14 THEME 主題 2 | Developing a Sustainable Environment 建設可持續發展的環境 Participating Institutions City University of Hong Kong The Hong Kong University of Science and Technology Southern University of Science and Technology University of Macau Vanderbilt University University of London 參與院校 香港城市大學 香港科技大學 南方科技大學 澳門大學 范德堡大學 倫敦大學
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