Innovative Needle-Free Influenza Vaccines Show Promise for Broad Protection

The University of Hong Kong's (HKUMed) School of Public Health has made a significant advancement in the development of needle-free, live-attenuated influenza vaccines (LAIV) that offer extensive protection against both human and avian virus strains. This groundbreaking work has garnered multiple patents and prestigious awards at the recent 50th International Exhibition of Inventions in Geneva, including the Saudi Innovation Excellence Prize and two Gold Medals.

Influenza remains a critical global health concern, placing immense strain on healthcare systems worldwide. Vaccination is recognized as the most effective method for preventing and controlling influenza outbreaks. However, conventional seasonal influenza vaccines typically target only three selected strains and necessitate annual updates, which can result in diminished efficacy if circulating viruses do not align with the selected strains. Moreover, current vaccines do not protect against infections caused by animal influenza viruses, including avian strains, which are considered a potential source of future pandemics. The World Health Organization (WHO) has underscored the urgent need for a new generation of universal influenza vaccines.

The research team has introduced two innovative strategies for developing next-generation LAIVs. The first method involves incorporating a human ?-1,3-galactosyltransferase gene into the human influenza virus genome. This modification allows infected cells to display ?-Gal epitopes on their surfaces. Since humans produce antibodies against ?-Gal, this encourages a more robust immune response, enhancing vaccine-induced immunological activities such as antibody-mediated cytotoxicity, opsonization, and phagocytosis.

In preclinical trials using mouse models, the vaccine demonstrated safety and was found to be non-pathogenic. The vaccinated mice exhibited strong immune responses, including both antibody and T-cell reactions, providing broad protection against various influenza A virus subtypes, including human H1N1 and H3N2, as well as avian H5N1 strains.

The second strategy employed by the research team involved introducing numerous silent mutations into the human influenza virus, transforming its codon usage to mimic that of avian influenza viruses. This alteration resulted in a virus that was attenuated in mammalian cells, making it a suitable candidate for LAIV. Notably, the modified virus was able to replicate effectively in chicken eggs, a crucial aspect of current vaccine production methods.

The expression of viral proteins in the LAIV remained consistent with that of the original wild-type virus, ensuring a strong immune response against various strains. In vitro and in vivo experiments confirmed that these attenuated viruses could serve as effective LAIVs, protecting vaccinated mice from infections caused by different subtypes of influenza A viruses, including both human and avian strains.

This advancement in LAIV technology marks a critical step toward developing more effective influenza vaccines that can provide comprehensive protection against a wide range of viral threats. The intranasal administration of LAIVs not only enhances mucosal immune responses along the respiratory tract but also reduces the anxiety associated with injections, particularly among young children, thereby addressing vaccine hesitancy.

Moving forward, the research team plans to utilize the resources provided by the Hong Kong Jockey Club Global Health Institute (HKJCGHI) to further develop these vaccines. Collaborative efforts with the International Vaccine Institute (IVI) are underway to ensure continued progress in vaccine research, with the expectation of conducting further studies that adhere to Good Laboratory Practice (GLP) standards.