HKUMed researchers develop the world's first organoid-based platform to evaluate the therapeutic potential of neutralising antibodies in the human body, providing more reliable scientific evidence for clinical treatment. The research team includes (from right): Professor Kelvin To Kai-wang, Professor Jane Zhou Jie and Dr Li Cun.
A research team from the Department of Microbiology under the School of Clinical Medicine in the LKS Faculty of Medicine of the University of Hong Kong (HKUMed), has successfully developed the world's first 'nasal organoid-based SARS-CoV-2 Neutralising Antibody Evaluation Platform'. The platform uses respiratory organoids that adequately model viral infection in the human respiratory tract, enabling accurate assessment of the effectiveness of antibodies and vaccines against SARS-CoV-2, the virus responsible for COVID-19.
Comparing the conventional cell line-based method usually used by the scientific community and the organoid platform developed by HKUMed, Professor Yuen Kwok-Yung, Chair of Infectious Diseases and Henry Fok Professor in Infectious Diseases, a contributor to the study, stated: 'Our study revolutionises the long-standing cell line-based methods for evaluating antibody neutralisation efficacy. By using respiratory organoids, we can evaluate the therapeutic potential of neutralising antibodies in the human body more accurately, providing more reliable scientific evidence for clinical treatment. We hope this innovation will become the new gold standard for measuring the efficacy of neutralising antibodies and vaccines against respiratory viruses.'
The US Food and Drug Administration (FDA) is actively promoting the adoption of organoid technology in drug development. Organoid-based preclinical safety and efficacy evaluations have great potential to fast-track antibody drug development. Professor Jane Zhou Jie, the Assistant Professor who led the research, explained: 'There is growing evidence showing that experiments using cell lines do not truly reflect the actual effects of antibodies in the human body. Establishing a platform that closely mimics human physiology is therefore crucial for advancing drug development.'
HKUMed's innovative platform is poised to become an essential tool for evaluating antiviral drugs and vaccines against respiratory viruses, accelerating the development of effective therapies. The research article entitled 'Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy' will be published in the latest issue of Proceedings of the National Academy of Sciences (PNAS).
Pioneering respiratory organoid culture system
In response to the global COVID-19 pandemic, which began in early 2020, scientists from around the world have rapidly developed monoclonal antibodies targeting the SARS-CoV-2 spike protein to block viral entry by preventing binding to the human ACE2 receptor. Many of these drugs have received emergency use authorisation for high-risk patients.
Since 2017, Professors Jane Zhou Jie, Department Chairperson Kelvin To Kai-wang, and Yuen Kwok-Yung have collaborated with Professor Hans Clevers of the Hubrecht Institute, a global leader in organoid research, to establish a respiratory organoid culture system using lung stem cells and nasal epithelial cells. Through continuous optimisation, the team developed standardised nasal , airway, and alveolar organoids, enabling the reconstruction and expansion of complete respiratory epithelial cells in laboratory settings. These organoids have become indispensable tools for respiratory disease research and drug development, offering highly reliable models that closely simulate the cellular composition and functionality of human respiratory tissues. The innovative respiratory organoid models and organoid-based applications won Gold Medals at the Geneva International Exhibition of Inventions in both 2023 and 2025.
Unlike traditional cell lines, these organoids faithfully simulate human airway tissues, offering a biologically relevant platform for evaluating antibody efficacy.
Precise evaluation to empower antibody and vaccine development
The research team has pioneered the use of nasal organoids to assess neutralising antibody activity. This novel method has proven to be more accurate than traditional cell experiments. For example, the antibody VIR-7831 showed limited effectiveness against Omicron variants in traditional cell line-based experiments, leading the FDA to revoke its clinical use. However, multiple clinical trials later demonstrated its effectiveness in preventing severe illness and death during the Omicron dominance. HKUMed's organoid platform mirrored these clinical outcomes, revealing strong antiviral activity conferred by VIR-7831 and related antibodies. Similarly, another group of S2-targeting antibodies, effective in animal experiments, showed significantly higher antiviral efficacy in organoids compared to cell line-based assays. Since the levels of viral receptor and protease in organoids closely resemble those found in human respiratory tissues, these respiratory organoids can accurately predict the clinical effectiveness of antibodies in humans. This not only improves the efficacy assessment of SARS-CoV-2 antibodies but also helps identify therapeutic antibodies and vaccines with real clinical potential, ultimately facilitating the development of other antiviral drugs and vaccines.
FDA promotes organoid technology to accelerate antibody development
The FDA announced a major policy shift in April this year, encouraging the use of organoid technology in drug development and outlining plans to phase out mandatory animal testing within three to five years. Professor Jane Zhou Jie commented, 'As the founding team of the organoid platform, we are committed to pushing the boundaries of respiratory organoid technology. Using models that more closely mimic human physiology, we aim to foster transformative advances in the development of antiviral antibody drugs and vaccines with more accurate and efficient evaluation tools.'
Professor Kelvin To Kai-wang concluded, 'Organoids will play a key role in the biomedical research and development of antiviral drugs and vaccines, further improving patient treatment outcomes and advancing scientific progress, ultimately contributing significantly to global public health.'
About the research team
The collaborative research team was led by Professor Jane Zhou Jie, Assistant Professor, and Professor Yuen Kwok-Yung, Chair of Infectious Diseases, and Henry Fok Professor in Infectious Diseases, both from the Department of Microbiology under the School of Clinical Medicine at HKUMed; and Professor Hans Clevers, Hubrecht Institute, the Netherlands. The study was conducted primarily by PhD student Wan Zhixin and Dr Li Cun, Research Assistant Professor.
Other researchers included Professor Chu Hin, Associate Professor; Professor Chen Zhiwei, Suen Chi-Sun Professor in Clinical Science and Chair Professor of Immunology and Immunotherapy; and Professor Kelvin To Kai-wang, Department Chairperson; all from the Department of Microbiology under the School of Clinical Medicine at HKUMed. Other team members also included Professor Liu Xiaojuan, Peking University Third Hospital; Professor Zhang Zheng, Shenzhen Third People's Hospital; and Professor Zhang Linqi, Tsinghua University.
