CVVT and HKUMed develop innovative organoid-based platform for precise evaluation of antibody and vaccine efficacy, accelerating FDA application of organoid technology

A collaborative research team from CVVT and the Department of Microbiology at the School of Clinical Medicine within the LKS Faculty of Medicine at the University of Hong Kong (HKUMed) has achieved a significant breakthrough by introducing the world's first 'nasal organoid-based SARS-CoV-2 Neutralising Antibody Evaluation Platform'. This innovative platform utilizes respiratory organoids that effectively model viral infections in the human respiratory tract, enabling precise evaluations of antibody and vaccine efficacy against SARS-CoV-2, the causative agent of COVID-19.

In a comparison between the conventional cell line-based methodology commonly employed by the scientific community and the organoid platform pioneered by the team, Professor Yuen Kwok-Yung, Managing Director of CVVT and a key contributor to the study, remarked, "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 advocating for the adoption of organoid technology in drug development processes. Organoid-based assessments of preclinical safety and efficacy hold immense promise in expediting the development of antibody-based drugs. Professor Jane Zhou Jie, the Principal Investigator of CVVT, spearheading the research, elucidated, "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."

This groundbreaking platform is poised to become an indispensable tool for evaluating antiviral medications and vaccines targeting respiratory viruses, thereby accelerating the creation of effective treatment modalities. The research paper titled Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy' is slated for publication in the upcoming issue of Proceedings of the National Academy of Sciences (PNAS) [Link to Publication].

Pioneering a respiratory organoid culture system

In response to the onset of the global COVID-19 pandemic in early 2020, researchers worldwide swiftly developed monoclonal antibodies that target the SARS-CoV-2 spike protein to impede viral entry by preventing binding to the human ACE2 receptor. Many of these therapeutic agents have received emergency use authorization for high-risk patients.

Since 2017, a collaborative effort with Professor Hans Clevers of the Hubrecht Institute, a renowned authority in organoid research, has facilitated the establishment of a respiratory organoid culture system utilizing lung stem cells and nasal epithelial cells. Through continual refinement, the team standardized nasal, airway, and alveolar organoids, enabling the recreation and expansion of complete respiratory epithelial cells in laboratory settings. These organoids have emerged as indispensable tools for researching respiratory diseases and drug development, providing highly reliable models that closely mirror the cellular composition and functions of human respiratory tissues. The innovative respiratory organoid models and their applications secured Gold Medals at the Geneva International Exhibition of Inventions in both 2023 and 2025.

In contrast to traditional cell lines, these organoids faithfully replicate human airway tissues, furnishing a biologically relevant platform for assessing antibody efficacy.

Precise evaluations to empower antibody and vaccine development

The research team has pioneered the utilization of nasal organoids for evaluating neutralizing antibody efficacy. This novel approach has proven to be more precise than conventional cell-based experiments. For instance, the antibody VIR-7831 exhibited limited efficacy against Omicron variants in traditional cell line-based tests, leading to its clinical use revocation by the FDA. However, subsequent clinical trials demonstrated its effectiveness in preventing severe illness and fatalities during the Omicron surge. Our organoid platform mirrored these clinical outcomes, showcasing robust antiviral activity conferred by VIR-7831 and related antibodies. Similarly, a group of S2-targeting antibodies, which displayed efficacy in animal studies, exhibited significantly heightened antiviral potency in organoids compared to cell line-based assays. As the levels of viral receptors and proteases in organoids closely resemble those in human respiratory tissues, these respiratory organoids can accurately forecast the clinical efficacy of antibodies in humans. This not only enhances the efficacy assessment of SARS-CoV-2 antibodies but also aids in identifying therapeutic antibodies and vaccines with genuine clinical potential, thereby expediting the development of other antiviral drugs and vaccines.

FDA endorses organoid technology for expediting antibody development

In a significant policy shift in April of this year, the FDA advocated for the utilization of organoid technology in drug development and outlined plans to phase out mandatory animal testing within three to five years. Professor Jane Zhou Jie remarked, "As pioneers of the organoid platform, we are dedicated to pushing the boundaries of respiratory organoid technology. By employing models that closely emulate human physiology, we strive to drive transformative advancements in the development of antiviral antibody drugs and vaccines through 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."