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
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