HKUMed has achieved a significant breakthrough in developing needle-free, live-attenuated influenza vaccines with broad protection against human and avian virus subtypes. The novel innovations resulted in multiple patents and impressive accolades at the 50th International Exhibition of Inventions Geneva 2025, including the Saudi Innovation Excellence Prize and two Gold Medals, one of which came with Congratulations of the Jury. (From right: Professor Leo Poon Lit-man and Dr Alex Chin Wing-hong)
A research team led by the School of Public Health in the LKS Faculty of Medicine, the University of Hong Kong (HKUMed), in collaboration with the Centre for Immunology & Infection (C2i), has achieved a significant breakthrough in developing broadly protective, live-attenuated influenza vaccines (LAIV). These innovative LAIV platforms offer potential to develop universal influenza vaccines that induce a more robust immune response against various virus subtypes, including both human and avian strains. These achievements have resulted in multiple patents and impressive accolades at the 50th International Exhibition of Inventions Geneva 2025, including the Saudi Innovation Excellence Prize and two Gold Medals, one of which came with Congratulations of the Jury.
Background
Influenza remains a major respiratory disease, which places a heavy burden on healthcare systems worldwide. Vaccination is the most efficient way to prevent and control influenza. Current seasonal influenza vaccines, however, protect primarily against three selected strains and require annual updates. Their efficacy can significantly decline if the circulating viruses do not match the strains chosen each year for each hemisphere. Moreover, these vaccines fail to guard against human infections caused by animal influenza viruses, such as avian strains, which pose a potential global pandemic threat. The World Health Organization (WHO) has underscored the urgent need for a new generation of universal influenza vaccines.
Research methods and findings
The research team developed two innovative approaches to create next-generation LAIVs. The first strategy involved inserting a human α-1,3-galactosyltransferase gene into the genome of a human influenza virus. This modification prompts infected host cells to express the α-Gal epitopes on their surface. Since humans naturally produce anti-α-Gal antibodies, this can allow preexisting antibody to recognise cells infected by the vaccine, thereby enhancing vaccine induced immune responses, including antibody-mediated cytotoxicity, opsonisation and phagocytosis. The research data showed that the vaccine is attenuated and is not pathogenic in mouse models. In experiments, vaccinated mice showed strong innate and adaptive immune responses, including antibody and T-cell responses. These immune responses conferred broad protection against various influenza A virus subtypes, including human H1N1 and H3N2, and avian H5N1 strains.
The second approach to developing next-generation LAIVs involved introducing hundreds of silent mutations to a human influenza virus, shifting its codon usage from that of a human influenza virus to that of an avian influenza virus-like pattern. This shift resulted in the attenuation of the virus in mammalian cells, making it safe for use as an LAIV. Additionally, the mutant virus replicated perfectly in chicken eggs, which is crucial for current effective vaccine manufacturing processes. With this approach, the viral protein expression of the LAIV remained identical to the original wildtype virus, providing a robust immune response against the viruses. The research team successfully generated several attenuated viruses with different human influenza virus backbones, including H1N1 and H3N2. The results of in vitro and in vivo experiments confirmed that these viruses were attenuated in mammalian hosts. They can thus be used as LAIVs to protect vaccinated mice from different subtypes of influenza A virus infection, including the human H1N1 and H3N2 viruses, as well as the avian H5N1 and H7N9 influenza viruses.
Significance of the research
The development of these two award-winning LAIVs represents a significant advancement in the quest for broadly protective and efficient influenza vaccines. This new generation of LAIVs can both protect humans from seasonal influenza viruses and address the threat posed by emerging viruses, like avian influenza viruses. 'The advantages of LAIVs lie in their intranasal administration, which has been shown to induce mucosal immune responses along the respiratory tract, providing additional protection against infection,' highlighted Professor Leo Poon Lit-man, Chair Professor of Public Health Virology and Head of the Division of Public Health Laboratory Sciences, School of Public Health, HKUMed. 'This needle-free delivery method alleviates the fear of vaccination, particularly in young children, so it will help mitigate vaccine hesitancy.'
Future development
These scientific breakthroughs represent a promising step towards a future in which influenza vaccines can offer comprehensive protection against a wide array of viral threats. Moving forward, the research team will leverage the international platform of the Hong Kong Jockey Club Global Health Institute (HKJCGHI) for further development, ensuring continued progress and making a global impact in this vital area.
'Both HKUMed and the International Vaccine Institute (IVI), one of the collaborators of the HKJCGHI, have initiated discussions and contributed intellectual input towards the vaccine development', remarked Professor Leo Poon Lit-man, who is also the Co-Director of HKJCGHI. 'It is anticipated that in the near future, further studies, including research work adhering to Good Laboratory Practice (GLP) standards, will be conducted through the resources of the Institute.'
About the research team
The research projects were led by Professor Leo Poon Lit-man, Daniel C K Yu Professor in Virology, Chair Professor of Public Health Virology and Head of the Division of Public Health Laboratory Sciences, School of Public Health, HKUMed; the Managing Director and Lead Scientist of the Centre for Immunology & Infection (C2i); the Co-Director of the Hong Kong Jockey Club Global Health Institute (HKJCGHI); and the Co-Director of the HKU-Pasteur Research Pole, HKUMed. Other members included Dr Alex Chin Wing-hong, School of Public Health, HKUMed; and the Centre for Immunology & Infection (C2i).
About the Centre for Immunology & Infection (C2i)
The Centre for Immunology & Infection (C2i) is the fruit of a long-standing partnership between the University of Hong Kong (HKU) and the Institut Pasteur, using novel technology platforms for biomarker discovery and the development of new vaccines and therapeutic strategies to address public health challenges and make Hong Kong a global centre of excellence for precision medicine and innovative interventions targeting emerging infectious diseases.
The Centre aims to characterise immune responses to infectious agents and their components in a healthy Asian population, and develop new vaccine platforms for influenza, new strategies to monitor mosquito-borne viruses and new treatments for lethal respiratory virus infections. More at www.c2i.hk
About the Hong Kong Jockey Club Global Health Institute (HKJCGHI)
The Hong Kong Jockey Club Global Health Institute (HKJCGHI) is a partnership between the University of Hong Kong (HKU), the University of Cambridge (UCAM), and the International Vaccine Institute (IVI). Established on 1 March 2024, with support from The Hong Kong Jockey Club Charities Trust, the Institute aims to enhance global pandemic preparedness through vaccine research, development, and implementation. HKJCGHI leverages the IVI's global field sites and vaccine expertise, HKU's leadership in virology and epidemiology, and UCAM's strength in optimising human immune responses. It unites world-leading scientists to foster collaboration and innovation in vaccine research and trains future global health leaders. More athttps://www.med.hku.hk/en/news/press/20231115-hkjcghi
Acknowledgements
The research projects were supported by the Health and Medical Research Fund of the Health Bureau of the HKSAR Government; and the Area of Excellence Scheme and Theme-based Research Scheme of The University Grants Committee of the HKSAR Government. The Centre for Immunology & Infection is supported by grants from InnoHK, an initiative of the Innovation and Technology Commission of the HKSAR Government.
