Breakthrough in Influenza Defense: Organoid-based Studies Reveal Cross-Protective NA Antibodies Against H5N1 Viruses

A groundbreaking study led by BiomOrgan Limited, a spin-off company from the Centre for Virology, Vaccinology and Therapeutics (CVVT), has leveraged its proprietary respiratory organoids to provide a novel platform for developing influenza vaccines and antibodies. They revealed a critical human immune mechanism that provides natural cross-protection against emerging H5N1 influenza viruses, including the cattle-associated clade 2.3.4.4b strain.

The study was spearheaded by Prof. Zhou Jie (Principal Investigator at CVVT and Associate Professor at HKUMed) and Prof. Yuen Kwok-Yung (Managing Director of CVVT and Chair Professor at HKUMed), alongside international collaborator Dr. Richard Webby from St. Jude Children’s Research Hospital. BiomOrgan has developed a revolutionary experimental platform using human respiratory organoids — miniature, lab-grown models of the human airway — to study influenza viruses. The study was published in Nature Communications  [link to publication].

The researchers report that neuraminidase (NA)-specific antibodies, commonly induced by seasonal H1N1 influenza infections or vaccinations, can strongly neutralize both the newly emerged 2.3.4.4b H5N1 virus and prior avian H5N1 strain. This discovery explains why, despite widespread infection in mammals such as dairy cattle, human cases remain rare and typically mild.

Crucially, this is the first time the protective activity conferred by influenza NA antibodies has been demonstrated using human respiratory organoids, which more accurately mimic the human respiratory system than traditional cell-based assays.

Why Traditional Methods Missed This Protection

Conventional influenza neutralization assays rely on immortalized cell lines such as MDCK cells. These cells lack the natural mucus layer present in the human respiratory tract, making them unable to detect NA antibody neutralizing activity.

Human respiratory organoids, however, recreate the entire respiratory epithelium and airway mucus environment, enabling direct measurement of NA-mediated neutralization for the first time. This breakthrough opens up a new experimental platform for evaluating influenza immunity and developing NA-targeted vaccines and therapeutics.

Major Scientific Findings

H5N1 Shows High Replication Fitness in Human Airway and Nasal Organoids

The team evaluated both the newly emerged 2.3.4.4b H5N1 strain and the prior avian H5N1 strain in human airway and nasal organoids. They found that 2.3.4.4b H5N1 replicates far more efficiently than avian H5N1.

Pre-existing NA Antibodies Strongly Neutralize H5N1 in Organoids

• Healthy individuals already possess NA antibodies capable of neutralizing H5N1

• Seasonal influenza vaccination further boosts these cross-protective antibodies

• Removing NA antibodies from serum eliminates the neutralization effect

Breakthrough: Long-term Expandable Bovine Airway & Mammary Organoids

The team also successfully established bovine airway and mammary gland organoids, enabling direct study of H5N1 infection in cattle tissues.

They found that:

• H5N1 replicates efficiently in bovine airway organoids

• H5N1 shows strong mammary gland tropism, matching real-world dairy farm outbreaks

These results confirm that N1-specific antibodies induced by seasonal H1N1 influenza provide natural cross-protection against H5N1, a mechanism that traditional cell-based assays fail to detect. These pre-existing NA antibodies counteract the high replication of 2.3.4.4b H5N1, protecting humans from infection. 

This suggests that respiratory transmission in cattle may be under-recognized, offering new insights into outbreak dynamics and informing future surveillance strategies.

Translating CVVT Innovation into Real-World Impact

This milestone underscores CVVT’s core mission: translating cutting-edge biomedical research into transformative public health solutions.

To bridge the gap between laboratory discovery and industrial application, BiomOrgan Limited is scaling these proprietary organoid platforms into organoid-based neutralization assays as a transformative tool for infectious disease research. It offers physiologically relevant organoid models and services to global pharmaceutical partners to accelerate the development of NA-targeted vaccines, therapeutics, and drug candidate evaluations.

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About the Research Team

The study was conducted by Prof. Zhou Jie, Prof. KY Yuen and colleagues from The University of Hong Kong and Dr. Richard Webby from St. Jude Children’s Research Hospital in the U.S., one of the world’s leading influenza experts.

Prof. Zhou Jie specializes in developing state-of-the-art organoid models of the human respiratory system, which have already earned international recognition for their innovative applications in infectious disease research. Her team’s work continues to push the boundaries of biomedical science, bridging the gap between laboratory research and real-world healthcare solutions.

About BiomOrgan Limited

Founded in 2021 by Prof. Zhou Jie, BiomOrgan is dedicated to transforming cutting‑edge organoid technology into practical solutions for drug discovery, vaccine development, and disease modeling. The company collaborates globally with pharmaceutical companies, research institutes, and medical institutions to deliver reliable, scalable organoid‑based products and services to the industry. BiomOrgan’s proprietary organoid platforms provide pharmaceutical partners with physiologically relevant models that traditional cell‑based systems cannot replicate, enabling more accurate evaluation of vaccines, antibodies, and antiviral candidates.

Enquiries: bd@biomorgan.hk

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.