CVVT Deputy Director Zhiwei Chen and HKUMed Researchers Invent a Novel Bispecific Antibody Drug Ambushing the Highly Pathogenic Influenza H5N1 and Diverse Subtypes

Researchers led by Professor Zhiwei Chen, CVVT Deputy Director and Head of the AIDS Institute, Department of Microbiology, School of Clinical Medicine, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), and the Center for Virology, Vaccinology and Therapeutics (CVVT) have invented a tandem bispecific antibody, M-SiaB. The invention involves a sialic acid-receptor anchoring strategy, which significantly enhances the potency and breadth of M-SiaB against not only diverse subtypes of influenza viruses (e.g. H1N1, H3N2, H5N1 and H7N9) in vitro but also nasal challenges by the authentic influenza H1N1/PR8 and the highly pathogenic avian influenza (HPAI) H5N1/Texas/2024 strains in animal models.

Critically, intranasal M-SiaB confers markedly enhanced protection against nasal challenges with the seasonal and avian influenza virus strains. This invention has recently won a gold medal at the 51st International Exhibition of Inventions of Geneva (2026). The research article is now published in the international scientific journal, Nature Communications  (Click here to view the journal article).

Background

In recent years, the clade 2.3.4.4b HPAI H5N1 has been particularly worrisome because the overall fatality rate of H5N1 is approximately 52% in humans to date. Although HPAI H5N1 viruses have not resulted in a major pandemic, the outbreak of HPAI H5N1/Texas/2024 virus, belonging to the clade 2.3.4.4b, has been reported in cattle herds and subsequently linked to 70 human cases, including one fatality since the spring of 2024. Vaccination remains one of the most effective modalities for protection. However, antigenic drift and shift frequently reduce the effectiveness of vaccines, highlighting the need for effective prophylactic and therapeutic drug interventions. Yet most existing NAbs have limited efficacy against genetically divergent pathogenic influenza viruses.

Research Findings

In this study, the HKUMed and CVVT team establish a sialic acid-anchoring strategy to engineer a sialic acid-anchored tandem M-SiaB antibody by fusing a hemagglutinin (HA) stalk-specific monoclonal NAb with a sialic acid receptor-binding domain (SiaB). 

Photo: The mode of M-SiaB action

M-SiaB shows 4- to 20-fold greater neutralizing potency against diverse authentic influenza viruses compared to the parental NAb and suppresses multiple stages of the viral life cycle, including viral attachment, entry and release. Importantly, intranasal M-SiaB confers markedly enhanced protection against nasal challenges with pathogenic H1N1/PR8 and the H5N1/Texas/2024 strains. Notably, a single dose of M‑SiaB maintains survival after a highly lethal H5N1/Texas/2024 challenge for up to 21 dayst

Significance of Study

‘Our strategy, the simultaneous blockade of influenza HA and its sialic acid receptor by our M‑SiaB, is useful for further improving the potency and breadth of bnAbs and warrants the clinical development of M‑SiaB for both prophylactic and therapeutic applications against genetically divergent, highly pathogenic influenza virus infection.’

- Professor Chen Zhiwei, Deputy Director of CVVT, Chair Professor of Immunology and Immunotherapy, Suen Chi-Sun Professor in Clinical Science at the Department of Microbiology, School of Clinical Medicine, HKUMed

‘The M-SiaB not only enhances the antiviral potency of the HA stalk-specific NAb but also increases its local retention within the respiratory tract, the primary site of viral infection and transmission. A single dose of M SiaB is able to provide complete protection for up to 21 days against cattle H5N1 infection induced death in an animal model, which is critical for improving suboptimal protection and preventing subsequent viral escape.'

- Professor ZHOU Runhong, Assistant Professor of the Department of Microbiology, HKUMed

Acknowledgements

This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20G, C1134-20G and C5110-20G); the Research Grants Council General Research Fund (17117422); the Wellcome Trust (P86433); the Health@InnoHK to CVVT, Innovation and Technology Commission of Hong Kong; Emergency Key Program of Guangzhou Laboratory (EKPG22-01); the donations from the Friends of Hope Education Fund; the Hong Kong Theme-Based Research Scheme (T12-703/23-N and T11-702/24-N); the National Science and Technology Major Project of the Ministry of Science and Technology of China (2025ZD01904502 and 2025ZD01900701); Health and Medical Research Fund (25240582) and the HKU seed fund (2403102004 and 2501263903). We would like to acknowledge the assistance of the Centre of PanorOmic Sciences of the University of Hong Kong Li Ka Sing Faculty of Medicine.

About the Research Team

The research team was led by Professor CHEN Zhiwei, Deputy Director of CVVT, Director of AIDS Institute, Chair Professor of Immunology and Immunotherapy, Suen Chi-Sun Professor in Clinical Science, HKUMed). The research work was conducted primarily by Dr Ruina Jin, Postdoc, Ms ALDUNGAROVA Aruzhan, PhD student, and Prof ZHOU Runhong, Assistant Professor, who shared the first authorship. 

This collaborative team also includes Dr Wang Pui, Scientific Officer; Dr ZHOU, Dongyan, Postdoc; Ms KIM Kyungmin, PhD student; Dr LIU Li, Scientific Officer; Ms LIU Na, PhD student; Ms CHEN Yuting, PhD student; Ms LEE Yelim, Research Assistant; Mr POON Vincent Kwok-Man, Senior Technical Officer; Mr CHAN Chris Chung-Sing, Senior Technical Officer; Ms JOSELYN Lucetta, PhD candidate; Prof CHEN Honglin, Professor; Prof YUEN Kwok-Yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, School of Clinical Medicine, HKUMed and Director of the State Key Laboratory of Emerging Infectious Diseases, HKU; Prof ZHOU Runhong, Prof CHAN Jasper Fuk-woo and Prof CHEN Zhiwei shared the correspondence authorship.

About the AIDS Institute and Department of Microbiology, School of Clinical Medicine, HKUMed

The academic staff of the Department of Microbiology are actively involved in clinical service and basic research. Postgraduate students may pursue studies on various aspects of microbiology and infectious diseases leading to an MPhil or PhD degree. The Master of Medical Sciences programme offers an opportunity to postgraduates interested in more in-depth studies on the biomedical aspects of clinical microbiology and infectious disease. In addition, the clinical staff of the Department also participate in the training of clinical microbiologists in Hong Kong and Shenzhen. The Infectious Disease Courses and Postgraduate Diploma Programme provide a unique avenue for the training of qualified medical practitioners in infectious diseases.

About the InnoHK Center for Virology, Vaccinology and Therapeutics (CVVT)

CVVT is an R&D Centre funded by the InnoHK initiative under the Innovation and Technology Commission (ITC) of the Government of Hong Kong Special Administrative Region of the People’s Republic of China. Led by renowned virologist Professor Yuen Kwok-Yung, the Centre brings together top international scientific research talents in the development of respiratory virus vaccines, antimicrobial agents, rapid diagnostics, and organoid modelling technology. It aims to proactively address emerging and re-emerging infectious disease threats by translating research into practical applications to mitigate their impact on public health and the economy.